Nutritional formulas comprising medium chain fatty acids or esters thereof and methods related thereto

ABSTRACT

This disclosure relates to nutritional formulas and uses for treating or preventing a gastrointestinal condition and/or motor-planning speech and/or coordinator difficulties. In certain embodiments, this disclosure relates to a nutritional formula comprising medium 5 chain fatty acids, or esters thereof (such as and tri-, di-, mono-glycerides, or alkyl esters), unsaturated fatty acids, and a vitamin E and optionally other nutrients. In certain embodiments, any of the compounds or nutrients may be in alternative salt forms.

CROSS-REFERENCE TO RELATED APPLICATIONS

This Application is the National Stage of International ApplicationNumber PCT/US2014/053990 filed Sep. 4, 2014, which claims priority toU.S. Provisional Application No. 61/873,865 filed Sep. 5, 2013. Theentirety of each of these applications is hereby incorporated byreference for all purposes.

BACKGROUND

Autism spectrum disorders (ASD) are typically defined by impairments inverbal and non-verbal communication, social interactions, and repetitivebehaviors. Gastrointestinal (GI) symptoms are common in individuals withASD. See Williams et al., PLoS ONE, 2011, 6(9): e24585. The total orpartial inability to plan verbal movement, common in autism spectrumdisorders, is diagnosed as verbal apraxia or dyspraxia. Morris & Aginreport that children with verbal apraxia responded to polyunsaturatedfatty acids and Vitamin E supplementation. Altern Ther Health Med, 2009,15(4):34-43. See also US Published Patent Application Number2008/0213239 and US 2009/0075862.

Intestinal lymphangiectasia is a rare disease that is characterized bylymphatic vessel dilation, diarrhea, and loss of protein and immunedysregulation. It is considered to be a chronic form of protein-losingenteropathy. Aoyagi et al. report that enteral nutrition appears to beas effective as total parenteral nutrition for human patients withintestinal lymphangiectasia. Digestive Diseases and Sciences, 2005,50(8):1467-1470.

McClave et al. report guidelines for the provision and assessment ofnutrition support therapy for adult critically ill patients. J ParenterEnteral Nutr, 2009, 33(3):277-316.

See also. U.S. Pat. Nos. 6,258,387, 5,922,766, and 4,959,350.

References cited herein are not an admission of prior art.

SUMMARY

This disclosure relates to nutritional formulas and uses for treating orpreventing a gastrointestinal condition and/or motor-planning speechand/or coordinator difficulties. In certain embodiments, this disclosurerelates to a nutritional formula comprising medium chain fatty acids, oresters thereof (such as and tri-, di-, mono-glycerides, or alkylesters), unsaturated fatty acids, and a vitamin E and optionally othernutrients. In certain embodiments, any of the compounds or nutrients maybe in alternative salt forms.

In certain embodiments, the disclosure relates to a dietary formulationcomprising: a) medium chain fatty acid, glycerol ester, or alkyl esterthereof, b) an omega-3 fatty acid, alkyl ester thereof, or glycerolester thereof, and c) a vitamin E isomer.

In certain embodiments, the glycerol ester of the medium chain fattyacid is selected from glycerol tricaprate, glycerol, dicaprate, glycerolmonocaprate, glycerol tricaprylate, glycerol dicaprylate, glycerolmonocaprylate, and glycerol trihexanoate, or combinations thereof.

In certain embodiments, the medium chain fatty acid or alkyl esterthereof is selected from capric acid, ethyl caprate, caprylic acid,ethyl caprylate, hexanoic acid, and ethyl hexanoate, or combinationsthereof.

In certain embodiments, the nutritional formula further comprises alauric acid or ester thereof selected from glycerol trilaurate, glyceroldilaurate, glycerol monolaurate, lauric acid, ethyl laurate, orsaturated or unsaturated fatty acid chains of greater than 12 carbons orcombinations thereof.

In certain embodiments, the nutritional formula comprises coconut oil,palm kernel oil or combinations thereof.

In certain embodiments, the omega-3 fatty acid or alkyl ester thereof isselected from alpha-linolenic acid, eicosapentaenoic acid,docosahexaenoic acid, ethyl linolenate, ethyl eicosapentaenoate, andethyl docosahexaenoate or combinations thereof. In certain embodiments,the formula comprises eicosapentaenoic acid and docosahexaenoic acid,wherein the ratio of eicosapentaenoic acid and docosahexaenoic acid isin a range of from about 1.5:1 to about 5:1.

In certain embodiments, the vitamin E isomer is selected fromalpha-tocopherol and gamma-tocopherol or a combination thereof, whereinthe alpha-tocopherol is present in an amount of from about 500 mg toabout 3000 mg per unit dose, and the gamma-tocopherol is present in anamount of from about 200 mg to about 1000 mg per unit dose.

In certain embodiments, the disclosure relates to a dietary formulationcomprising: a) medium chain fatty acid, glycerol ester, or alkyl esterthereof, b) an omega-3 fatty acid, alkyl ester thereof, or glycerolester thereof, c) a vitamin E isomer and d) a vitamin K.

In certain embodiments, the disclosure relates to a dietary formulationcomprising medium chain fatty acid, glycerol ester, or alkyl esterthereof, eicosapentaenoic acid, docosahexaenoic acid, alpha tocopherol,gamma tocopherol, phytonadione, and gamma-linolenic acid.

In certain embodiments, the disclosure relates to a dietary formulationcomprising: a) medium chain fatty acid, glycerol ester, or alkyl esterthereof, b) an omega-3 fatty acid, alkyl ester thereof, or glycerolester thereof, c) a vitamin A isomer, d) a vitamin D, e) vitamin Eisomer and f) a vitamin K.

In certain embodiments, the disclosure relates to a dietary formulationcomprising medium chain fatty acid, glycerol ester, or alkyl esterthereof, eicosapentaenoic acid, docosahexaenoic acid, retinoic acid,cholecalciferol, ergocalciferol, alpha tocopherol, gamma tocopherol,phytonadione, and gamma-linolenic acid.

In certain embodiments, the formula comprises further comprises acomponent selected from long chain fatty acids, esters of long chainfatty acids, alpha-lipoid acid, a carnitine, probiotics, an omega-6fatty acid, an esters of omega-6 fatty acid, gamma-linolenic acid, ethylgamma-linolenate, an omega-9 fatty acid, esters of omega-9 fatty acid,oleic acid, ethyl oleate, zinc, calcium, magnesium, selenium, a vitaminA, a vitamin B₁, a vitamin B₂, a vitamin B₃, a vitamin B₅, a vitamin B₆,a vitamin B₇, a vitamin B₉, a vitamin B₁₂, vitamin C, vitamin D, vitaminK, S-adenosylmethionine, a phosphocholine, creatine, a coenzyme Q,taurine, tetrahydrobiopterin, methylcobalamin, betaine, pancreaticenzymes, folinic acid, pancrelipase, a leukotriene inhibitor, aarginine, glutamine, N-acetylcysteine, an anti-fungal agent, berberine,an anti-inflammatory agent, anti-bacterial agent, anti-oxidant,saccharides and polysaccharides or combinations thereof.

In certain embodiments, the formulation is in a dosage form selectedfrom a tablet, a capsule, a powder, a gel, and a liquid. In certainembodiments, dietary formulas disclosed herein comprise one or morefood-grade components.

In certain embodiments, the disclosure relates to a dietary formulationcomprising: a) medium chain fatty acid, glycerol ester, or alkyl esterthereof, b) an omega-3 fatty acid, alkyl ester thereof, or glycerolester thereof, and c) a vitamin E isomer. In certain embodiments theomega-3 ester is the ethyl ester of eicosapentaenoic acid. In certainembodiments, the medium chain fatty glycol ester is a mixture of glycolesters of caprylic acid and capric acid. In certain embodiments, theratio of glycerol esters of caprylic acid and capric acid is 1:1 to 4:1,or 1:1 to 5:1, or 1:1.5 to 1:3 by weight respectively.

In certain embodiments, the formula further comprises berberine andpancreatic enzymes.

In certain embodiments, the formula further comprises L-amino acids andnot peptides or proteins.

In certain embodiments, the disclosure relates to a dietary formulationcomprising formulations reported herein in combination with a source ofglucose, malodextrin, cornstarch, or combinations thereof. In certainembodiments, the formula further comprises monosaccharides such asglucose, fructose, and galactose and optionally disaccharides, buttypically not larger polysaccharides. In certain embodiments, thisformulation is contemplated for subjects with fructose malabsorption ora primary lactase deficiency that is genetic due to environmentalcauses.

In certain embodiments, the disclosure relates to a dietary formulationcomprising formulations reported herein in combination with5-hydroxytryptophan present in an amount of from about 10 mg to about100 mg per unit dose, sulforaphane present in an amount of from about500 μg to about 5000 μg per unit dose, curcumin present in an amount offrom about 50 mg to about 2500 mg per unit dose, or combinationsthereof.

In certain embodiments, the disclosure relates to a dietary formulationcomprising formulations reported herein in combination with L-aminoacids and not peptides or proteins. In certain embodiments, theformulation does not contain phenylalanine.

In certain embodiments, the disclosure relates to a dietary formulationcomprising formulations reported herein in combination with a probioticor berberine.

In certain embodiments, the disclosure relates to a dietary formulationcomprising formulations reported herein in combination with iron presentin an amount of from about 2.5-10 mg per unit dose, phosphorus presentin an amount of from about 200-850 mg per unit dose, iodine present inan amount of from about 30-120 μg per unit dose, copper present in anamount of from about 0.25-1.0 mg per unit dose, manganese present in anamount of from about 0.5-2.0 mg per unit dose, chromium present in anamount of from about 10-45 μg per unit dose, molybdenum present in anamount of from about 15-100 μg per unit dose, inositol present in anamount of from about 10-1000 mg per unit dose, or combinations thereof.

In certain embodiments, the disclosure relates to methods of treating orpreventing apraxia and/or autism spectrum disorder, the methodcomprising orally administering to an individual in need thereof aneffective amount of a dietary formula disclosed herein. In certainembodiments, the disclosure relates to methods the subject is diagnosedwith intestinal lymphangiectasia.

In certain embodiments, the disclosure relates to methods of treating orpreventing small bowel inflammation and conditions lending to smallbowel bacterial overgrowth that induce fat malabsorption, the methodcomprising orally administering to an individual in need thereof aneffective amount of a dietary formula disclosed herein to a subject inneed thereof.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 shows video pill cam indicating erythema and white nodules in thejejunum. The white villi and/or spots (dilated lacteals), white nodulesin the jejunum are observed on video capsule endoscopy are consistentwith the diagnosis of intestinal lymphangiectasia. This taken togetherwith a long-standing history of fat malabsorption, neurological symptomsof vitamin E deficiency, a protein-losing enteropathy with previouslyunexplained hypoalbuminemia, multiple micronutrient and vitamindeficiencies (zinc, iron, vitamin D, B12 etc), short stature, edema ofthe ankles and hands, hypocholesterolemia (cholesterol<100), andvulnerability to infections suggesting immune dysregulation (chronicthrush, disseminated molluscum contagiosum, recurrent skin, ear andsinus infections) explains the dramatic response to nutritionalinterventions in this child.

DETAILED DISCUSSION

Before the present disclosure is described in greater detail, it is tobe understood that this disclosure is not limited to particularembodiments described, and as such may, of course, vary. It is also tobe understood that the terminology used herein is for the purpose ofdescribing particular embodiments only, and is not intended to belimiting, since the scope of the present disclosure will be limited onlyby the appended claims.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this disclosure belongs. Although any methods andmaterials similar or equivalent to those described herein can also beused in the practice or testing of the present disclosure, the preferredmethods and materials are now described.

All publications and patents cited in this specification are hereinincorporated by reference as if each individual publication or patentwere specifically and individually indicated to be incorporated byreference and are incorporated herein by reference to disclose anddescribe the methods and/or materials in connection with which thepublications are cited. The citation of any publication is for itsdisclosure prior to the filing date and should not be construed as anadmission that the present disclosure is not entitled to antedate suchpublication by virtue of prior disclosure. Further, the dates ofpublication provided could be different from the actual publicationdates that may need to be independently confirmed.

As will be apparent to those of skill in the art upon reading thisdisclosure, each of the individual embodiments described and illustratedherein has discrete components and features which may be readilyseparated from or combined with the features of any of the other severalembodiments without departing from the scope or spirit of the presentdisclosure. Any recited method can be carried out in the order of eventsrecited or in any other order that is logically possible.

Embodiments of the present disclosure will employ, unless otherwiseindicated, techniques of medicine, organic chemistry, biochemistry,molecular biology, pharmacology, and the like, which are within theskill of the art. Such techniques are explained fully in the literature.

It must be noted that, as used in the specification and the appendedclaims, the singular forms “a,” “an,” and “the” include plural referentsunless the context clearly dictates otherwise. Thus, for example,reference to “an omega-3 fatty acid” includes a plurality of such fattyacids and reference to “the vitamin E” includes reference to one or morevitamin E isoforms and equivalents thereof known to those skilled in theart, and so forth. It is further noted that the claims may be drafted toexclude any optional element. As such, this statement is intended toserve as antecedent basis for use of such exclusive terminology as“solely,” “only” and the like in connection with the recitation of claimelements, or use of a “negative” limitation.

In this specification and in the claims that follow, reference will bemade to a number of terms that shall be defined to have the followingmeanings unless a contrary intention is apparent.

Prior to describing the various embodiments, the following definitionsare provided and should be used unless otherwise indicated.

As used herein, “subject” refers to any animal, typically a humanpatient, livestock, or domestic pet such as a dog.

As used herein, the terms “prevent” and “preventing” include theprevention of the recurrence, spread or onset. It is not intended thatthe present disclosure be limited to complete prevention. In someembodiments, the onset is delayed, or the severity of the disease orcondition is reduced.

As used herein, the terms “treat” and “treating” are not limited to thecase where the subject (e.g., patient) is cured and the disease iseradicated. Rather, embodiments, of the present disclosure alsocontemplate treatment that merely reduces symptoms, and/or delaysdisease progression.

As used herein, the term “combination with” when used to describeadministration with an additional treatment means that the agent may beadministered prior to, together with, or after the additional treatment,or a combination thereof.

“Fatty acids” refers to a family of carboxylic acids having a saturatedor unsaturated hydrocarbon chain of about 4 to about 28 carbons inlength, and is intended to include carboxylic acid salt forms.

Medium chain fatty acids (MCFAs) refer to a family of carboxylic acidshaving a saturated or unsaturated hydrocarbon chain of from about 6 to10 carbons in length, and is intended to include carboxylic acid saltforms. Examples include capric acid, caprylic acid, and hexanoic acid.Medium-chain triglycerides (MCTs) are esters (tri-, di-, monoglycerideesters) of medium chain fatty acids and glycerol. Natural sources ofMCFAs and MCTs include coconut, palm kernel oil, and bovine milk. Onemethod of producing MCT is by hydrolysis of coconut or palm kernel oil,filtration of MCFAs, and subsequent re-esterification of the MCFAs withglycerol. Oils produced by re-esterification contain mostly caprylicacid (octanoic) and capric acid (decanoic acid), at a ratio from about50:50 to 80:20 with typically less than 5% of long chain or shorterchain acids.

Long chain fatty acids are typically between 12 and 28 carbons inlength. Unsaturated fatty acids have at least one carbon-carbon doublebond in the hydrocarbon chain. Unsaturated fatty acids includemonounsaturated fatty acids and polyunsaturated fatty acids (PUFAs).Unsaturated fatty acids are designated by the position of the firstdouble bond from the methyl end of the hydrocarbon chain.

Omega-3 fatty acids have a first double bond at the third carbon fromthe methyl end of the chain; and include, e.g., alpha-linolenic acid(octadeca-9,12,15-trienoic acid), stearidonic acid(octadeca-6,9,12,15-tetraenoic acid), eicosapentaenoic acid(eicosa-5,8,11,14,17-pentaenoic acid; “EPA”), docosapentaenoic acid(docosa-7,10,13,16,19-pentaenoic acid), eicosatetraenoic acid(eicosa-8,11,14,17-tetraenoic acid), and docosahexaenoic acid(docosa-4,7,10,13,16,19-hexaenoic acid; “DHA”). Ethyl eicosapentaenoate,icosapent ethyl (Vascepa™) is an omega-3 polyunsaturated fatty acid(PUFA) ester composition FDA approved for the treatment ofhypertriglyceridemia.

Omega-6 fatty acids have a first double bond at the sixth carbon fromthe methyl end of the chain; and include, e.g., linoleic acid(9,12-octadecadienoic acid), gamma-linolenic acid(6,9,12-octadecatrienoic acid; GLA), eicosadienoic acid(11,14-eicosadienoic acid), dihomo-gamma-linolenic acid(8,11,14-eicosatrienoic acid), arachidonic acid(5,8,11,14-eicosatetraenoic acid), docosadienoic acid(13,16-docosadienoic acid), adrenic acid (7,10,13,16-docosatetraenoicacid), docosapentaenoic acid (4,7,10,13,16-docosapentaenoic acid), andcalendic acid (8E,10E,12Z-octadecatrienoic acid), and the like. Omega-9fatty acids have a first double bond at the ninth carbon from the methylend of the chain; and include, e.g., oleic acid (cis-9-octadecenoicacid); eicosenoic acid (cis-11-eicosenoic acid); mead acid(all-cis-5,8,11-eicosatrienoic acid); erucic acid (cis-13-docosenoicacid); and nervonic acid (cis-15-tetracosenoic acid).

As used herein, a “vitamin E” refers to a family of eight moleculeshaving a chromanol ring (chroman ring with an alcoholic hydroxyl group)and a 12-carbon aliphatic side chain containing two methyl groups in themiddle and two more methyl groups at the end. The side chain of thetocopherols is saturated, while the side chain of the tocotrienolscontain three double-bonds, all of which adjoin a methyl group. Thetocopherols and the tocotrienols exist in four isoforms, referred to asalpha, beta, gamma and delta isoforms. The isoforms are named on thebasis of the number and position of the methyl groups on the chromanolring. The alpha form has three methyl groups, the beta and gamma formshave two methyl groups and the delta for has only one methyl group. A“vitamin E” may be alpha-tocopherol, beta-tocopherol, gamma-tocopherol,alpha-tocotrienol, beta-tocotrienol, and gamma-tocotrienol. A “vitaminE” also includes esters of a vitamin E isoform. For example, a “vitaminE” includes esters of a tocopherol, including acetates and succinates.

As used herein, “alkyl” means a noncyclic straight chain or branched,unsaturated or saturated hydrocarbon such as those containing from 1 to10 carbon atoms. Representative saturated straight chain alkyls includemethyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-septyl, n-octyl,n-nonyl, and the like; while saturated branched alkyls includeisopropyl, sec-butyl, isobutyl, tert-butyl, isopentyl, and the like.Unsaturated alkyls contain at least one double or triple bond betweenadjacent carbon atoms (referred to as an “alkenyl” or “alkynyl”,respectively). Representative straight chain and branched alkenylsinclude ethylenyl, propylenyl, 1-butenyl, 2-butenyl, isobutylenyl,1-pentenyl, 2-pentenyl, 3-methyl-1-butenyl, 2-methyl-2-butenyl,2,3-dimethyl-2-butenyl, and the like; while representative straightchain and branched alkynyls include acetylenyl, propynyl, 1-butyryl,2-butyryl, 1-pentynyl, 2-pentynyl, 3-methyl-1-butyryl, and the like.

As used herein, the term a “lipoic acid” refers to alpha-lipoic acid,which is a chiral molecule also known as 6,8-dithioloctanoic acid.Unless specified the term “lipoic acid” encompasses the racemic mixtureas well as any other (non-50/50) mixture of the enantiomers includingsubstantially pure forms of either the R-(+) or the S-(−) enantiomer.Further, unless specified otherwise the term covers salts (e.g. Na and Ksalts) and amides, esters and metabolites of the acid.

“Carnitine” is also known as 3-hydroxy-4-(trimethylazaniumyl)butanoate.As used herein, the term a “carnitine” includes carnitine and “carnitineanalogs” and encompasses racemic or essentially pure L-carnitine(carnitine), or a corresponding alkanoyl-carnitine such asacetyl-carnitine or propionyl-carnitine, or a suitable salt of suchcompounds such as L-carnitine tartrate, L-carnitine fumarate,L-carnitine-magnesium-citrate, acetyl-L-carnitine tartrate,acetyl-L-carnitine-magnesium-citrate, or any mixture of theaforementioned compounds.

Formulations

The present disclosure provides for dietary formulations comprisingmedium chain fatty acids, or esters thereof, such as and tri-, di-,monoglycerides, or alkyl esters, unsaturated fatty acids such as omega 3fatty acids, and a vitamin E and optionally other nutrients.

Suitable medium chain fatty acids, or esters thereof, such as and tri-,di-, monoglycerides, or alkyl esters include glycerol tricaprate,glycerol, dicaprate, glycerol monocaprate, glycerol tricaprylate,glycerol dicaprylate, glycerol monocaprylate, and glycerol trihexanoate,capric acid, ethyl caprate, caprylic acid, ethyl caprylate, hexanoicacid, and ethyl hexanoate, or combinations thereof.

It is contemplated that these medium chain fatty acids may be obtainedfrom coconut oil and palm kernel oil. For example, some processes ofabstracting medium chain fatty acids from coconut oil result incompositions containing medium chain fatty acids and glycerol esterswith about 3% caproic acid, and about 65% caprylic acid, and capric acid30%, and about less than 1% lauric acid and other long chain fattyacids. In certain embodiments, the nutritional formula further comprisesa lauric acid or ester thereof selected from glycerol trilaurate,glycerol dilaurate, glycerol monolaurate, lauric acid, ethyl laurate, orsaturated or unsaturated fatty acid chains of greater than 12 carbons orcombinations thereof. Typically the lauric acid and other long chainfatty acids are less than 2% or less than 1% by weight total weight offatty acids.

Suitable unsaturated fatty acids include, but are not limited to,omega-3 fatty acids and omega-6 fatty acids. Suitable omega-3 fattyacids include, e.g., a-linolenic acid (octadeca-9,12,15-trienoic acid),stearidonic acid (octadeca-6,9,12,15-tetraenoic acid), eicosapentaenoicacid (eicosa-5,8,11,14,17-pentaenoic acid; “EPA”), docosapentaenoic acid(docosa-7,10,13,16,19-pentaenoic acid), eicosatetraenoic acid(eicosa-8,11,14,17-tetraenoic acid), and docosahexaenoic acid(docosa-4,7,10,13,16,19-hexaenoic acid; “DHA”). Suitable omega-6 fattyacids include, e.g., linoleic acid (9,12-octadecadienoic acid),gamma-linolenic acid (6,9,12-octadecatrienoic acid; GLA), eicosadienoicacid (11,14-eicosadienoic acid), dihomo-gamma-linolenic acid(8,11,14-eicosatrienoic acid), arachidonic acid(5,8,11,14-eicosatetraenoic acid), docosadienoic acid(13,16-docosadienoic acid), adrenic acid (7,10,13,16-docosatetraenoicacid), docosapentaenoic acid (4,7,10,13,16-docosapentaenoic acid), andcalendic acid (8E,10E,12Z-octadecatrienoic acid).

A contemplated formulation can comprise one, two, three, four, five,six, seven, or eight different vitamin E isoforms. For example, in someembodiments, a subject formulation comprises alpha-tocopherol andgamma-tocopherol; and substantially no other vitamin E isoforms. Inother embodiments, a subject formulation includes alpha-tocopherol,gamma-tocopherol, and at least one other vitamin E isoform. For example,in some embodiments, a subject formulation includes alpha-tocopherol,gamma-tocopherol, and at least one of beta-tocopherol, delta-tocopherol,alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol, anddelta-tocotrienol. In other embodiments, a subject formulation includesalpha-tocopherol, gamma-tocopherol, beta-tocopherol, delta-tocopherol,alpha-tocotrienol, beta-tocotrienol, gamma-tocotrienol, anddelta-tocotrienol.

In some embodiments, a contemplated formulation comprises at least onemedium chain fatty acid or ester, at least one omega-3 fatty acid; andat least one vitamin E isoform. In some embodiments, a contemplatedformulation comprises two different omega-3 fatty acids. In someembodiments, a contemplated formulation comprises eicosapentaenoic acid(EPA); docosahexaenoic acid (DHA); and at least one vitamin E isoform.In certain embodiments, the ratio of EPA to DHA can range from about1.5:1 (EPA:DHA) to about 5:1 (EPA:DHA), where the ratio is on a weightbasis. For example, the EPA:DHA ratio can range from about 1.5:1 toabout 2:1, from about 2:1 to about 2.5:1, from about 2.5:1 to about 3:1,from about 3:1 to about 3.5:1, from about 3.5:1 to about 4:1, from about4:1 to about 4.5:1, or from about 4.5:1 to about 5:1. In someembodiments, the EPA:DHA ratio is 2.5:1. When considering weight ratiosof salts the, non-salt form is contemplated.

In some embodiments, a contemplated formulation comprises at least onemedium chain fatty acid or ester or at least two medium chain fatty acidor ester; at least one omega-3 fatty acids; at least one vitamin Eisoform; and at least one omega-6 fatty acid. For example, in someembodiments, a contemplated formulation comprises medium chain fattyacids or esters or coconut oil; EPA; DHA; and at least one omega-6 fattyacid. In some embodiments, a contemplated formulation comprises mediumchain fatty acids or esters or coconut oil; EPA; DHA; at least onevitamin E isoform; and gamma-linolenic acid (GLA). In some embodiments,a contemplated formulation comprises medium chain fatty acids or estersor coconut oil; EPA; DHA; alpha-tocopherol; gamma-tocopherol; and GLA.

In some embodiments, a contemplated formulation comprises medium chainfatty acids or esters or coconut oil; at least two different omega-3fatty acids; at least one vitamin E isoform; and an omega-9 fatty acid.In some embodiments, a contemplated formulation comprises medium chainfatty acids or esters or coconut oil; at least two different omega-3fatty acids; at least one vitamin E isoform; an omega-6 fatty acid; andan omega-9 fatty acid. The omega-9 fatty acid is in some embodiments amonounsaturated fatty acid. In some embodiments, the omega-9 fatty acidis oleic acid.

Lipoic Acid

In some embodiments, a contemplated formulation comprises medium chainfatty acids or esters or coconut oil and a lipoic acid. Thus, e.g., insome embodiments, a contemplated formulation comprises medium chainfatty acids or esters or coconut oil; a long chain fatty acid or ester;at least one vitamin E isoform; and alpha-lipoic acid. In someembodiments, a contemplated formulation comprises medium chain fattyacids or esters or coconut oil; at least one omega-3 fatty acid; atleast one vitamin E isoform; and alpha-lipoic acid. For example, in someembodiments, a contemplated formulation comprises medium chain fattyacids or esters or coconut oil; EPA; DHA; at least one vitamin Eisoform; and alpha-lipoic acid. In some embodiments, a contemplatedformulation comprises medium chain fatty acids or esters or coconut oil;EPA; DHA; alpha-tocopherol; gamma-tocopherol; and alpha-lipoic acid. Inother embodiments, a contemplated formulation comprises medium chainfatty acids or esters or coconut oil; at least one omega-3 fatty acid;an omega-6 fatty acid; at least one vitamin E isoform; and alpha-lipoicacid. For example, in some embodiments, a contemplated formulationcomprises medium chain fatty acids or esters or coconut oil; EPA; DHA;GLA; alpha-tocopherol; gamma-tocopherol; and alpha-lipoic acid.

The alpha-lipoic acid can exist as an about 50/50 or racemic mixture ofR-(+)-alpha-lipoic acid and S-(−)-alpha-lipoic acid. The alpha-lipoicacid ingredient of a contemplated formulation can be about 100% R-(+)enantiomer. However, the alpha-lipoic acid can be present in acontemplated formulation in any mixture of the two enantiomers e.g. 10%S-(−) and 90% R-(+); 25% S-(−) and 75% R-(+); etc.

Carnitine

In some embodiments, a contemplated formulation comprises medium chainfatty acids or esters or coconut oil and carnitine. Thus, e.g., in someembodiments, a contemplated formulation comprises medium chain fattyacids or esters or coconut oil; long chain fatty acid; at least onevitamin E isoform; and carnitine. In some embodiments, a contemplatedformulation comprises medium chain fatty acids or esters or coconut oil;at least one omega-3 fatty acid; at least one vitamin E isoform; andcarnitine. For example, in some embodiments, a contemplated formulationcomprises medium chain fatty acids or esters or coconut oil; EPA; DHA;at least one vitamin E isoform; and carnitine. In some embodiments, acontemplated formulation comprises medium chain fatty acids or esters orcoconut oil; EPA; DHA; alpha-tocopherol; gamma-tocopherol; andcarnitine. In other embodiments, a contemplated formulation comprisesmedium chain fatty acids or esters or coconut oil; at least one omega-3fatty acid; an omega-6 fatty acid; at least one vitamin E isoform; andcarnitine. For example, in some embodiments, a contemplated formulationcomprises medium chain fatty acids or esters or coconut oil; EPA; DHA;GLA; alpha-tocopherol; gamma-tocopherol; and carnitine. In otherembodiments, a contemplated formulation comprises medium chain fattyacids or esters or coconut oil; at least one omega-3 fatty acid; anomega-6 fatty acid; an omega-9 fatty acid; at least one vitamin Eisoform; and carnitine. For example, in some embodiments, a contemplatedformulation comprises medium chain fatty acids or esters or coconut oil;EPA; DHA; GLA; oleic acid; alpha-tocopherol; gamma-tocopherol; andcarnitine.

In some embodiments, the carnitine component of a contemplatedformulation is 90%-100% L-carnitine (or a salt thereof). In otherembodiments, the carnitine component of a contemplated formulation is90%-100% acetyl-carnitine. In other embodiments, the carnitine componentof a contemplated formulation is a mixture of L-carnitine (or a saltthereof) and acetyl-carnitine. For example, in some embodiments, thecarnitine component of a contemplated formulation can comprise 10%L-carnitine and 90% acetyl-carnitine; 15% L-carnitine and 85%acetyl-carnitine; 20% L-carnitine and 80% acetyl-carnitine; 25%L-carnitine and 75% acetyl-carnitine; 30% L-carnitine and 70%acetyl-carnitine; 40% L-carnitine and 60% acetyl-carnitine; 50%L-carnitine and 50% acetyl-carnitine; 60% L-carnitine and 40%acetyl-carnitine; 70% L-carnitine and 30% acetyl-carnitine; 75%L-carnitine and 25% acetyl-carnitine; 80% L-carnitine and 20%acetyl-carnitine; 85% L-carnitine and 15% acetyl-carnitine; or 90%L-carnitine and 10% acetyl-carnitine; or L-carnitine andacetyl-carnitine in any other proportion, where the percentages are byweight.

Probiotics

A “probiotic” is a bacterium wherein the bacterium typically confers ahealth benefit. Lactobacillus and Bifidobacterium are common probiotics.Examples of probiotics include Lactobacillus rhamnosus, Lactobacillusplantarum, Lactobacillus casei, Lactobacillus acidophilus,Bifidobacterium infantis, Bifidobacterium animalis, and Escherichia coliNissle 1917,

In some embodiments, a contemplated formulation comprises medium chainfatty acids or esters or coconut oil and a probiotic (e.g.,Lactobacillus rhamnosus). Thus, e.g., in some embodiments, acontemplated formulation comprises medium chain fatty acids or esters orcoconut oil; long chain fatty acid; at least one vitamin E isoform; anda probiotic. In some embodiments, a contemplated formulation comprisesmedium chain fatty acids or esters or coconut oil; at least one omega-3fatty acid; at least one vitamin E isoform; and a probiotic. Forexample, in some embodiments, a contemplated formulation comprisesmedium chain fatty acids or esters or coconut oil; EPA; DHA; at leastone vitamin E isoform; and a probiotic. In some embodiments, acontemplated formulation comprises medium chain fatty acids or esters orcoconut oil; EPA; DHA; alpha-tocopherol; gamma-tocopherol; and aprobiotic. In other embodiments, a contemplated formulation comprisesmedium chain fatty acids or esters or coconut oil; at least one omega-3fatty acid; an omega-6 fatty acid; at least one vitamin E isoform; and aprobiotic. For example, in some embodiments, a contemplated formulationcomprises medium chain fatty acids or esters or coconut oil; EPA; DHA;GLA; alpha-tocopherol; gamma-tocopherol; and a probiotic. In otherembodiments, a contemplated formulation comprises medium chain fattyacids or esters or coconut oil; at least one omega-3 fatty acid; anomega-6 fatty acid; an omega-9 fatty acid; at least one vitamin Eisoform; and a probiotic. For example, in some embodiments, acontemplated formulation comprises medium chain fatty acids or esters orcoconut oil; EPA; DHA; GLA; oleic acid; alpha-tocopherol;gamma-tocopherol; and a probiotic.

Amounts

The amounts in a contemplated formulation of medium chain fatty acids oresters or coconut oil; long chain fatty acids; and a vitamin E, as wellas the amounts of additional components such as carnitine andalpha-lipoic acid, can vary according to various factors, including,e.g., the age of the individual, the weight of the individual, thegenetic makeup of the individual, and the severity of symptoms exhibitedby the individual to whom a formulation is administered. The followingare general guidelines. Amounts are given as per unit dose.

Where a contemplated formulation includes medium chain fatty acids, oresters thereof, the medium chain fatty acids, or esters thereof arepresent in amount of from about 100 mg to about 5000 mg, e.g., fromabout 100 mg to about 200 mg, from about 200 mg to about 300 mg, fromabout 300 mg to about 400 mg, from about 400 mg to about 500 mg, fromabout 500 mg to about 600 mg, from about 600 mg to about 700 mg, fromabout 700 mg to about 800 mg, from about 800 mg to about 900 mg, fromabout 900 mg to about 1000 mg, from about 1000 mg to about 1100 mg, fromabout 1100 mg to about 1200 mg, from about 1200 mg to about 1300 mg,from about 1300 mg to about 1400 mg, from about 1400 mg to about 1500mg, from about 1500 mg to about 1600 mg, from about 1600 mg to about1700 mg, from about 1700 mg to about 1800 mg, from about 1800 mg toabout 1900 mg, from about 1900 mg to about 2000 mg, from about 2000 mgto about 2500 mg, from about 2500 mg to about 3000 mg, from about 3000mg to about 3500 mg, from about 3500 mg to about 4000 mg, from about4000 mg to about 4500 mg, or from about 4500 mg to about 5000 mg perunit dose, where the amounts given are for individual comprising mediumchain fatty acids, or esters thereof or for total comprising mediumchain fatty acids, or esters thereof (e.g., where more than onecomprising medium chain fatty acids, or esters thereof is present).

Where a contemplated formulation includes omega-3 fatty acids, theomega-3 fatty acids are present in amount of from about 100 mg to about5000 mg, e.g., from about 100 mg to about 200 mg, from about 200 mg toabout 300 mg, from about 300 mg to about 400 mg, from about 400 mg toabout 500 mg, from about 500 mg to about 600 mg, from about 600 mg toabout 700 mg, from about 700 mg to about 800 mg, from about 800 mg toabout 900 mg, from about 900 mg to about 1000 mg, from about 1000 mg toabout 1100 mg, from about 1100 mg to about 1200 mg, from about 1200 mgto about 1300 mg, from about 1300 mg to about 1400 mg, from about 1400mg to about 1500 mg, from about 1500 mg to about 1600 mg, from about1600 mg to about 1700 mg, from about 1700 mg to about 1800 mg, fromabout 1800 mg to about 1900 mg, from about 1900 mg to about 2000 mg,from about 2000 mg to about 2500 mg, from about 2500 mg to about 3000mg, from about 3000 mg to about 3500 mg, from about 3500 mg to about4000 mg, from about 4000 mg to about 4500 mg, or from about 4500 mg toabout 5000 mg per unit dose, where the amounts given are for individualomega-3 fatty acids or for total omega-3 fatty acids (e.g., where morethan one omega-3 fatty acid is present).

For example, in some embodiments, a contemplated formulation comprisesthe omega-3 fatty acids EPA and DHA. In some embodiments, a contemplatedformulation will comprise EPA in an amount of from about 500 mg to about3000 mg, e.g., from about 500 mg to about 600 mg, from about 600 mg toabout 700 mg, from about 700 mg to about 800 mg, from about 800 mg toabout 900 mg, from about 900 mg to about 1000 mg, from about 1000 mg toabout 1500 mg, from about 1500 mg to about 2000 mg, from about 2000 mgto about 2500 mg, or from about 2500 mg to about 3000 mg per unit dose;and will comprise DHA in an amount of from about 100 mg to about 400 mg,e.g., from about 100 mg to about 150 mg, from about 150 mg to about 200mg, from about 200 mg to about 250 mg, from about 250 mg to about 300mg, from about 300 mg to about 350 mg, or from about 350 mg to about 400mg per unit dose.

Where a contemplated formulation comprises the omega-3 fatty acids EPAand DHA, the ratio of EPA to DHA can range from about 1.5:1 (EPA:DHA) toabout 5:1 (EPA:DHA), where the ratio is on a weight basis. For example,the EPA:DHA ratio can range from about 1.5:1 to about 2:1, from about2:1 to about 2.5:1, from about 2.5:1 to about 3:1, from about 3:1 toabout 3.5:1, from about 3.5:1 to about 4:1, from about 4:1 to about4.5:1, or from about 4.5:1 to about 5:1. In some embodiments, acontemplated formulation comprises EPA and DHA in a ratio of 2.5:1EPA:DHA.

The amount of vitamin E present in a subject formulation can beexpressed in units (International Units, or IU), or in milligrams. Inthe past, the U.S. Dietary Reference Intake (DRI) Recommended DietaryAllowances (RDA) of vitamin E were expressed in Units. This “units” termhas been replaced in recent years by alpha-tocopherol equivalents(“alpha-TE”) or milligrams. One Unit is equivalent to 1 mg ofdl-alpha-tocopherol acetate or 0.6 mg d-alpha-tocopherol. Throughoutthis specification, amounts of vitamin E are given in mg.

The alpha-tocopherol and gamma-tocopherol isoforms of vitamin E can bepresent in a contemplated formulation in an amount of from about 100 mgto about 10,000 mg, e.g., from about 100 mg to about 200 mg, from about200 mg to about 300 mg, from about 300 mg to about 400 mg, from about400 mg to about 500 mg, from about 500 mg to about 600 mg, from about600 mg to about 700 mg, from about 700 mg to about 800 mg, from about800 mg to about 900 mg, from about 900 mg to about 1000 mg, from about1000 mg to about 2000 mg, from about 2000 mg to about 3000 mg, fromabout 3000 mg to about 3000 mg, from about 4000 mg to about 5000 mg,from about 5000 mg to about 6000 mg, from about 6000 mg to about 7000mg, from about 7000 mg to about 8000 mg, from about 8000 mg to about9000 mg, or from about 9000 mg to about 10,000 mg per unit dose, wherethe amounts given are for individual isoforms of vitamin E. In someembodiments, the alpha-tocopherol is d-alpha-tocopherol.

In some embodiments, a contemplated formulation includesalpha-tocopherol in an amount of from about 500 mg to about 3000 mg perunit dose, e.g., in an amount of from about 500 mg, from about 500 mg toabout 600 mg, from about 600 mg to about 700 mg, from about 700 mg toabout 800 mg, from about 800 mg to about 900 mg, from about 900 mg toabout 1000 mg, from about 1000 mg to about 2000 mg, or from about 2000mg to about 3000 mg per unit dose; and gamma-tocopherol in an amount offrom about 200 mg to about 1000 mg per unit dose, e.g., in an amount offrom about 200 mg to about 300 mg, from about 300 mg to about 400 mg,from about 400 mg to about 500 mg, from about 500 mg to about 600 mg,from about 600 mg to about 700 mg, from about 700 mg to about 800 mg,from about 800 mg to about 900 mg, or from about 900 mg to about 1000 mgper unit dose. In some of these embodiments, the formulation does notinclude vitamin E isoforms other than alpha-tocopherol andgamma-tocopherol. In other embodiments, the formulation includes, inaddition to alpha-tocopherol and gamma-tocopherol, at least oneadditional vitamin E isoform.

In some embodiments, a contemplated formulation includesalpha-tocopherol and gamma-tocopherol; and does not include othervitamin E isoforms. In other embodiments, a contemplated formulationincludes alpha-tocopherol and gamma-tocopherol; and one or moreadditional isoforms of vitamin E. Where a contemplated formulationincludes alpha-tocopherol and gamma-tocopherol, the alpha-tocopherol canbe present in an amount of from about 500 mg to about 10,000 mg, e.g.,from about 500 mg to about 1000 mg, from about 1000 mg to about 2000 mg,from about 2000 mg to about 3000 mg, from about 3000 mg to about 3000mg, from about 4000 mg to about 5000 mg, from about 5000 mg to about6000 mg, from about 6000 mg to about 7000 mg, from about 7000 mg toabout 8000 mg, from about 8000 mg to about 9000 mg, or from about 9000mg to about 10,000 mg; and the gamma-tocopherol can be present in anamount of from about 100 mg to about 1000 mg, e.g., from about 100 mg toabout 200 mg, from about 200 mg to about 300 mg, from about 300 mg toabout 400 mg, from about 400 mg to about 500 mg, from about 500 mg toabout 600 mg, from about 600 mg to about 700 mg, from about 700 mg toabout 800 mg, from about 800 mg to about 900 mg, or from about 900 mg toabout 1000 mg per unit dose.

Other forms of vitamin E (e.g., beta-tocopherol, delta-tocopherol,alpha-tocotrienol, beta-tocotrienol, delta-tocotrienol, andgamma-tocotrienol), if present in a contemplated formulation, can bepresent in an amount of from about 5 mg to about 2000 mg, e.g., fromabout 5 mg to about 10 mg, from about 10 mg to about 25 mg, from about25 mg to about 50 mg, from about 50 mg to about 75 mg, from about 75 mgto about 100 mg, from about 100 mg to about 125 mg, from about 125 mg toabout 150 mg, from about 150 mg to about 175 mg, or from about 175 mg toabout 200 mg, from about 200 mg to about 250 mg, from about 250 mg toabout 500 mg, from about 500 mg to about 750 mg, from about 750 mg toabout 1000 mg, from about 1000 mg to about 1250 mg, from about 1250 mgto about 1500 mg, from about 1500 mg to about 1750 mg, or from about1750 mg to about 2000 mg per unit dose, where the amounts given are forthe individual isoforms of vitamin E.

Where a contemplated formulation comprises one or more omega-6 fattyacids, the omega-6 fatty acid can be present in the formulation in anamount of from about 50 mg to about 500 mg, e.g., from about 50 mg toabout 75 mg, from about 75 mg to about 100 mg, from about 100 mg toabout 150 mg, from about 150 mg to about 200 mg, from about 200 mg toabout 250 mg, from about 250 mg to about 300 mg, from about 300 mg toabout 350 mg, from about 350 mg to about 400 mg, from about 400 mg toabout 450 mg, or from about 450 mg to about 500 mg per unit dose.

Where a contemplated formulation comprises one or more omega-9 fattyacids, the omega-9 fatty acid can be present in a subject formulation inan amount of from about 50 mg to about 500 mg, e.g., from about 50 mg toabout 75 mg, from about 75 mg to about 100 mg, from about 100 mg toabout 150 mg, from about 150 mg to about 200 mg, from about 200 mg toabout 250 mg, from about 250 mg to about 300 mg, from about 300 mg toabout 350 mg, from about 350 mg to about 400 mg, from about 400 mg toabout 450 mg, or from about 450 mg to about 500 mg per unit dose.

Where a subject formulation comprises alpha-lipoic acid, thealpha-lipoic acid can be present in a subject formulation in an amountof from about 50 mg to about 1000 mg, e.g., from about 50 mg to about 75mg, from about 75 mg to about 100 mg, from about 100 mg to about 150 mg,from about 150 mg to about 200 mg, from about 200 mg to about 250 mg,from about 250 mg to about 300 mg, from about 300 mg to about 350 mg,from about 350 mg to about 400 mg, from about 400 mg to about 450 mg,from about 450 mg to about 500 mg, from about 500 mg to about 600 mg,from about 600 mg to about 700 mg, from about 700 mg to about 800 mg,from about 800 mg to about 900 mg, or from about 900 mg to about 1000 mgper unit dose.

Where a subject formulation comprises carnitine, the carnitine can bepresent in a subject formulation in an amount of from about 150 mg toabout 3000 mg, e.g., from about 150 mg to about 200 mg, from about 200mg to about 250 mg, from about 250 mg to about 300 mg, from about 300 mgto about 350 mg, from about 350 mg to about 400 mg, from about 400 mg toabout 450 mg, from about 450 mg to about 500 mg, from about 500 mg toabout 600 mg, from about 600 mg to about 700 mg, from about 700 mg toabout 800 mg, from about 800 mg to about 900 mg, from about 900 mg toabout 1000 mg, from about 1000 mg to about 1250 mg, from about 1250 mgto about 1500 mg, from about 1500 mg to about 1750 mg, from about 1750mg to about 2000 mg, from about 2000 mg to about 2250 mg, from about2250 mg to about 2500 mg, from about 2500 mg to about 2750 mg, or fromabout 2750 mg to about 3000 mg per unit dose.

Additional Components

In certain embodiments, the disclosure relates to a dietary formulationcomprising: a) medium chain fatty acid, glycerol ester, phospholipidester, or alkyl ester thereof, b) an omega-3 fatty acid, alkyl esterthereof, or glycerol ester thereof, and c) a vitamin E isomer andadditional components. In certain embodiments, the additional componentsare selected from long chain fatty acids, esters of long chain fattyacids, alpha-lipoic acid, carnitine, an omega-6 fatty acid, esters ofomega-6 fatty acid, gamma-linolenic acid, ethyl gamma-linolenate, anomega-9 fatty acid, esters of omega-9 fatty acid, oleic acid, ethyloleate, zinc, calcium, magnesium, selenium, a vitamin A, a vitamin B₁, avitamin B₂, a vitamin B₃, a vitamin B₅, a vitamin B₆, a vitamin B₇, avitamin B₉, a vitamin B₁₂, vitamin C, vitamin D, vitamin K,S-adenosylmethionine, a phosphocholine, creatine, a coenzyme Q, taurine,tetrahydrobiopterin, methylcobalamin, betaine, pancreatic enzymes,folinic acid, pancrelipase, a leukotriene inhibitor, a arginine,glutamine, N-acetylcysteine, an anti-fungal agent, berberine, ananti-inflammatory agent, anti-bacterial agent, anti-oxidant, saccharidesand polysaccharides or combinations thereof.

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone vitamin E isoform; and one, two, three, four, five, six, seven,eight, nine, ten, 11, 12, 13, 14, 15, 16, 17, 18, 19, or more or all of:long chain fatty acids, esters of long chain fatty acids, alpha-lipoicacid, carnitine, an omega-6 fatty acid, esters of omega-6 fatty acid,gamma-linolenic acid, ethyl gamma-linolenate, an omega-9 fatty acid,esters of omega-9 fatty acid, oleic acid, ethyl oleate, zinc, calcium,magnesium, selenium, a vitamin A, a vitamin B₁, a vitamin B₂, a vitaminB₃, a vitamin B₅, a vitamin B₆, a vitamin B₇, a vitamin B₉, a vitaminB₁₂, vitamin C, vitamin D, vitamin K, S-adenosylmethionine, aphosphocholine, creatine, a coenzyme Q, taurine, tetrahydrobiopterin,methylcobalamin, betaine, pancreatic enzymes, folinic acid,pancrelipase, a leukotriene inhibitor, a arginine, glutamine,N-acetylcysteine, an anti-fungal agent, berberine, an anti-inflammatoryagent, anti-bacterial agent, anti-oxidant, saccharides andpolysaccharides or combinations thereof.

In some embodiments, a contemplated formulation includes a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; a vitamin E; and one or more amino acids.In some embodiments, a contemplated formulation includes an anti-fungalagent (e.g., imidozoles and triazoles, nystatin, amphotericin B etc). Insome embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; avitamin E; and an anti-inflammatory agent. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; a vitamin E; and an agent thatreduces oxidative stress.

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone vitamin E isoform; and a pancreatic enzyme. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one vitamin E isoform;and a leukotriene inhibitor. In some embodiments, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one vitamin E isoform; and a mastcell stabilizer (e.g., cromolyn). In other embodiments, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one vitamin E isoform; apancreatic enzyme; and a leukotriene inhibitor. For example, in someembodiments, a contemplated formulation comprising medium chain fattyacids, or esters thereof; an omega-3 fatty acid (e.g., EPA; DHA; or acombination of EPA and DHA, as described above; vitamin E (e.g.,alpha-tocopherol and gamma-tocopherol); alpha-lipoic acid; carnitine; apancreatic enzyme; and a leukotriene inhibitor.

Any minerals in a subject formulation can be present in salt form. Suchsalts can be carbonate, oxide, hydroxide, chloride, sulfate, phosphate,gluconate, lactate, acetate, fumarate, citrate, malate, amino acids, andthe like for the cationic minerals and sodium, potassium, calcium,magnesium, and the like for the anionic minerals.

Zinc

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and zinc. In some embodiments, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of vitamin E;carnitine; and zinc. In other embodiments, a contemplated formulationcomprises medium chain fatty acids, or esters thereof; an omega 3 fattyacid or ester; at least one isoform of vitamin E; alpha-lipoic acid; andzinc.

Zinc can be present in a subject formulation in the form of zincgluconate, zinc sulfate, zinc chloride, or any salt of zinc. Zinc can bepresent in a subject formulation in an amount of from about 5 mg toabout 50 mg, from about 5 mg to about 10 mg, from about 10 mg to about15 mg, from about 15 mg to about 20 mg, from about 20 mg to about 25 mg,from about 25 mg to about 30 mg, from about 30 mg to about 40 mg, orfrom about 40 mg to about 50 mg total daily dose or per unit dose.

Calcium

In some embodiments, a contemplated formulation comprising medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and calcium. In some embodiments, acontemplated formulation comprising medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; carnitine; and calcium. In other embodiments, a contemplatedformulation comprising medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of vitamin E;alpha-lipoic acid; and calcium.

Calcium can be present in a subject formulation in the form of calciumcarbonate, calcium citrate, calcium glubionate, calcium gluconate,calcium lactate, dibasic calcium phosphate, tribasic calcium phosphate,calcium acetate, and the like.

Calcium can be present in a subject formulation in an amount of fromabout 40 mg to about 2000 mg, from about 40 mg to about 100 mg, fromabout 100 mg to about 250 mg, from about 250 mg to about 500 mg, fromabout 500 mg to about 750 mg, from about 750 mg to about 1000 mg, fromabout 1000 mg to about 1500 mg, or from about 1500 mg to about 2000 mgtotal daily dose or per unit dose.

Magnesium

In some embodiments, a contemplated formulation comprising medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and magnesium. In some embodiments, acontemplated formulation comprising medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; carnitine; and magnesium. In other embodiments, a contemplatedformulation comprising medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of vitamin E;alpha-lipoic acid; and magnesium.

Magnesium can be present in a formulation as magnesium oxide, magnesiumcitrate, magnesium chloride, magnesium gluceptate, magnesium hydroxide,magnesium gluconate, magnesium lactate, magnesium pidolate, magnesiumsulfate, and the like. Magnesium can be present in a subject formulationin an amount of from about 50 mg to about 1000 mg, from about 50 mg toabout 75 mg, from about 75 mg to about 100 mg, from about 100 mg toabout 150 mg, from about 150 mg to about 200 mg, from about 200 mg toabout 250 mg, from about 250 mg to about 300 mg, from about 300 mg toabout 350 mg, from about 350 mg to about 400 mg, or from about 400 mg toabout 1000 mg total daily dose or per unit dose.

Selenium

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and selenium. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; carnitine; and selenium. In other embodiments, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of vitamin E;alpha-lipoic acid; and selenium.

Selenium can be present in the form of sodium selenate, sodium selenite,selenomethionine, and the like. Selenium can be present in a subjectformulation in an amount of from about 20 μg to about 500 μg, from about20 μg to about 30 μg, from about 30 μg to about 40 μg, from about 40 μgto about 50 μg, from about 50 μg to about 75 μg, from about 75 μg toabout 100 μg, from about 100 μg to about 150 μg, from about 150 μg toabout 200 μg, from about 200 μg to about 250 μg, from about 250 μg toabout 300 μg, from about 300 μg to about 350 μg, from about 350 μg toabout 400 μg, or from about 400 μg to about 500 μg total daily or unitdose.

Vitamin A

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and a vitamin A. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of avitamin E; carnitine; and a vitamin A. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; alpha-lipoic acid; and a vitamin A.

A “vitamin A” includes retinol, retinal (retinaldehyde), and retinoicacid; nor-retinoids; retro-retinoids; seco-retinoids (e.g.,1,6-seco-1,2-didehydroretinol); substituted retinoids (e.g.,5,6-Epoxy-5,6-dihydroretinol; ethyl 12-fluororetinoate; etc.); andanalogs such as 3-hydroxyretinol, 3-hydroxyretinoic acid,3-hydroxyretinal, 4-oxoretinol, 4-oxoretinoic acid, 4-oxoretinal,3,4-didehydroretinol (vitamin A₂), 3,4-didehydroretinoic acid,3,4-didehydroretinal, 4,5-didehydro-5,6-dihydroretinol, acycloretinol,acycloretinoic acid, and acycloretinal; and esters of vitamin A, e.g.,an acetate ester, a succinate ester, a palmitate ester, etc.

A vitamin A can be present in a contemplated formulation in an amount offrom about 200 IU to about 10,000 IU, e.g., 200 IU to about 250 IU, fromabout 250 IU to about 500 IU, from about 500 IU to about 1000 IU, fromabout 1000 IU to about 2000 IU, from about 2000 IU to about 3000 IU,from about 3000 IU to about 4000 IU, from about 4000 IU to about 5000IU, from about 5000 IU to about 7500 IU, or from about 7500 IU to about10,000 IU total daily dose.

Vitamin B₁

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and a vitamin B₁. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; carnitine; and a vitamin B₁. In other embodiments, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of vitamin E;alpha-lipoic acid; and a vitamin B₁.

A “vitamin B₁” includes thiamine (also referred to as “thiamin”); thehydrochloride and nitrate salts of thiamine; and thiamine alkyldisulfides such as thiamine propyldisulfide, thiamine tetrahydrofurfuryldisulfide, and thiamine o-benzoyl disulfide; neopyrithiamine;oxyneopyrithiamine; and the like.

A vitamin B₁ can be present in a subject formulation in an amount offrom about 0.05 mg to about 15 mg, from about 0.05 mg to about 0.1 mg,from about 0.1 mg to about 1.0 mg, from about 1.0 mg to about 1.5 mg,from about 1.5 mg to about 2.0 mg, from about 2.0 mg to about 2.5 mg,from about 2.5 mg to about 5 mg, from about 5 mg to about 7.5 mg, fromabout 7.5 mg to about 10 mg, from about 10 mg to about 12.5 mg, or fromabout 12.5 mg to about 15 mg total daily dose or per unit dose.

Vitamin B₂

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of a vitamin E; and a vitamin B₂. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of avitamin E; carnitine; and a vitamin B₂. In other embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of avitamin E; alpha-lipoic acid; and a vitamin B₂.

A “vitamin B₂” includes riboflavin; crystalline riboflavin coenzymeforms of riboflavin such as flavin adenine dinucleotide, flavin adeninemononucleotide, riboflavin 5-phosphate and their salts. Vitamin B₂ canbe present in a subject formulation in an amount of from about 0.05 mgto about 15 mg, from about 0.05 mg to about 0.1 mg, from about 0.1 mg toabout 1.0 mg, from about 1.0 mg to about 1.5 mg, from about 1.5 mg toabout 2.0 mg, from about 2.0 mg to about 2.5 mg, from about 2.5 mg toabout 5 mg, from about 5 mg to about 7.5 mg, from about 7.5 mg to about10 mg, from about 10 mg to about 12.5 mg, or from about 12.5 mg to about15 mg total daily dose or per unit dose.

Vitamin B₃

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and a vitamin B. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; carnitine; and vitamin B₃. In other embodiments, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of vitamin E;alpha-lipoic acid; and vitamin B₃.

A “vitamin B₃” includes niacin, niacinamide, nicotinamide adeninedinucleotide, and nicotinamide adenine dinucleotide phosphate. A vitaminB₃ can be present in a subject formulation in an amount of from about0.5 mg to about 200 mg, from about 0.5 mg to about 1 mg, from about 1 mgto about 10 mg, from about 10 mg to about 25 mg, from about 25 mg toabout 50 mg, from about 50 mg to about 75 mg, from about 75 mg to about100 mg, from about 100 mg to about 150 mg, or from about 150 mg to about200 mg.

Vitamin B₅

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and a vitamin B₅. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; carnitine; and vitamin B₅. In other embodiments, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of vitamin E;alpha-lipoic acid; and a vitamin B₅.

A “vitamin B₅” is also referred to as pantothenic acid, and encompassessalts such as calcium pantothenate; pantothenol; and panthenol. VitaminB₅ can be present in a completed formulation in an amount of from about0.4 mg to about 800 mg, from about 0.4 mg to about 1 mg, from about 1 mgto about 10 mg, from about 10 mg to about 25 mg, from about 25 mg toabout 50 mg, from about 50 mg to about 100 mg, from about 100 mg toabout 200 mg, from about 200 mg to about 300 mg, from about 300 mg toabout 400 mg, from about 400 mg to about 500 mg, from about 500 mg toabout 600 mg, from about 600 mg to about 700 mg, or from about 700 mg toabout 800 mg total daily dose or per unit dose.

Vitamin B₆

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of a vitamin E; and a vitamin B₆. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of avitamin E; carnitine; and a vitamin B₆. In other embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of avitamin E; alpha-lipoic acid; and a vitamin B₆.

A “vitamin B₆” includes pyridoxine, pyridoxal, pyridoxamine; andhydrochloride salts or 5-phosphates of pyridoxine, pyridoxamine, orpyridoxal. For example, pyridoxine hydrochloride can be included in acontemplated formulation.

A vitamin B₆ can be present in a contemplated formulation in an amountof from about 2 mg to about 250 mg, from about 2 mg to about 5 mg, fromabout 5 mg to about 10 mg, from about 10 mg to about 25 mg, from about25 mg to about 50 mg, from about 50 mg to about 75 mg, from about 75 mgto about 100 mg, from about 100 mg to about 125 mg, from about 125 mg toabout 150 mg, from about 150 mg to about 175 mg, from about 175 mg toabout 200 mg, from about 200 mg to about 225 mg, or from about 225 mg toabout 250 mg total daily dose or per unit dose.

Vitamin B₇

In some embodiments, a contemplated formulation comprising medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of a vitamin E; and a vitamin B₇. In some embodiments, acontemplated formulation comprising medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of avitamin E; a carnitine; and vitamin B₇. In other embodiments, acontemplated formulation comprising medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; alpha-lipoic acid; and vitamin B₇.

A “vitamin B₇” includes biotin, oxybiotin, biocytin, biotinol,D-homobiotin, D-norbiotin, dethiobiotin, biotin sulfone, biotin diaminesulfate, and the like. Vitamin B₇ can be present in a subjectformulation in an amount of from about 10 μg to about 800 μg, from about10 μg to about 25 μg, from about 25 μg to about 50 μg, from about 50 μgto about 100 μg, from about 100 μg to about 200 μg, from about 200 μg toabout 300 μg, from about 300 μg to about 400 μg, from about 400 μg toabout 500 μg, from about 500 μg to about 600 μg, from about 600 μg toabout 700 μg, or from about 700 μg to about 800 μg total daily dose orper unit dose.

Vitamin B₉

In some embodiments, a contemplated formulation comprising medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of a vitamin E; and a vitamin B₉. In some embodiments, acontemplated formulation comprising medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of avitamin E; carnitine; and a vitamin B₉. In other embodiments, acontemplated formulation comprising medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; alpha-lipoic acid; and a vitamin B₉.

A “vitamin B₉” (also known as pteroyl-L-glutamic acid; or folic acid)includes folic acid and any chemical derivative of folic acid thatfunction equivalently to folic acid, such as mono and polyglutamylfolates, dihydro and tetrahydro folates, methyl and formyl folates, andany isomer of a folate, e.g., an isomer of a reduced folate. Thus, e.g.,“folic acid” includes dihydrofolic acid, tetrahydrofolic acid,5-formyltetrahydrofolic acid, 10-formyltetrahydrofolic acid, 5-10methylenetetrahydrofolic acid, 5-10 methenyltetrahydrofolic acid,5-methyltetrahydrofolic acid, and derivatives of any of the foregoing;and a natural isomer of reduced folate, such as (6S)-tetrahydrofolicacid, 5-methyl-(6S)-tetrahydrofolic acid, 5-formyl-(6S)-tetrahydrofolicacid, 10-formyl-(6R)-tetrahydrofolic acid,5,10-methylene-(6R)-tetrahydrofolic acid,5,10-methenyl-(6R)-tetrahydrofolic acid,5-formimino-(6S)-tetrahydrofolic acid, and polyglutamyl derivatives ofany of the foregoing. Derivatives of folic acid include the precursors(pro-vitamins), metabolites, derivatives, and conjugates of the parentcompound, any of which may be either naturally occurring or synthetic;as well as the salts of the compounds.

A vitamin B₉ can be present in a subject formulation in an amount offrom about 200 μg to about 1000 μg, e.g., from about 200 μg to about 400μg, from about 400 μg to about 500 μg, from about 500 μg to about 600μg, from about 600 μg to about 700 μg, from about 700 μg to about 800μg, from about 800 μg to about 900 μg, or from about 900 μg to about1000 μg total daily dose or per unit dose.

Vitamin B₁₂

In some embodiments, a contemplated formulation comprising medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of a vitamin E; and a vitamin B₁₂. In some embodiments, acontemplated formulation comprising medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of avitamin E; carnitine; and a vitamin B₁₂. In other embodiments, acontemplated formulation comprising medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of avitamin E; alpha-lipoic acid; and a vitamin B₁₂.

A “vitamin B₁₂” refers to vitamin B₁₂ (cyanocobalamin) and itspharmaceutical derivatives, such as methylcobalamin, hydroxocobalamin,cyano-10-chlorocobalamin, aquocobalamin perchlorate,aquo-10-chlorocobalamin perchlorate, azidocobalamin, chlorocobalamin,cobalamin, methylcobalamin, adenosylcobalamin, and hydroxocobalamin.

A vitamin B₁₂ can be present in a contemplated formulation in an amountof from about 2 μg to about 1000 μg, 2 μg to about 10 μg, from about 10μg to about 25 μg, from about 25 μg to about 50 μg, from about 50 μg toabout 100 μg, from about 100 μg to about 200 μg, from about 200 μg toabout 300 μg, from about 300 μg to about 400 μg, from about 400 μg toabout 500 μg, from about 500 μg to about 600 μg, from about 600 μg toabout 700 μg, from about 700 μg to about 800 μg, from about 800 μg toabout 900 μg, or from about 900 μg to about 1000 μg total daily dose orper unit dose.

Vitamin C

In some embodiments, a contemplated formulation comprising medium chainfatty acids, or esters thereof; long chain fatty acid or ester; (e.g.,an omega-3 fatty acid or ester and/or an omega-6 fatty acid or ester);at least one isoform of a vitamin E; and a vitamin C. In someembodiments, a contemplated formulation comprises medium chain fattyacids, or esters thereof; an omega 3 fatty acid or ester; at least oneisoform of a vitamin E; carnitine; and a vitamin C. In otherembodiments, a contemplated formulation comprises medium chain fattyacids, or esters thereof; an omega 3 fatty acid or ester; at least oneisoform of a vitamin E; alpha-lipoic acid; and a vitamin C.

A “vitamin C” includes all forms of ascorbic acid, such as L-ascorbicacid, D-ascorbic acid, DL-ascorbic acid, D-araboascorbic acid,dehydroascorbic acid, xyloascorbic acid, esters of ascorbic acid, saltsof ascorbic acid, and the like.

A vitamin C can be present in a subject formulation in an amount of fromabout 80 mg to about 1000 mg, from about 80 mg to about 100 mg, fromabout 100 mg to about 200 mg, from about 200 mg to about 250 mg, fromabout 250 mg to about 300 mg, from about 300 mg to about 400 mg, fromabout 400 mg to about 500 mg, from about 500 mg to about 600 mg, fromabout 600 mg to about 700 mg, from about 700 mg to about 800 mg, fromabout 800 mg to about 900 mg, or from about 900 to about 1000 mg totaldaily dose or per unit dose.

Vitamin D

In some embodiments, a contemplated formulation comprising medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of a vitamin E; and a vitamin D. In some embodiments, acontemplated formulation comprising medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of avitamin E; carnitine; and a vitamin D. In other embodiments, acontemplated formulation comprising medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of avitamin E; alpha-lipoic acid; and a vitamin D.

A “vitamin D” includes, e.g., cholecalciferol (D3), ergocalciferol (D2),and biologically active metabolites and precursors such as, e.g.,1-alpha-hydroxy Vitamin D, 25-hydroxy Vitamin D, 1,25-dihydroxy VitaminD, and the like.

A vitamin D can be present in a subject formulation in an amount of fromabout 200 mg to about 2000 mg, 200 IU to about 2000 IU, from about 200IU to about 300 IU, from about 300 IU to about 400 IU, from about 400 IUto about 500 IU, from about 500 IU to about 600 IU, from about 600 IU toabout 700 IU, or from about 700 IU to about 2000 IU total daily dose orper unit dose.

Vitamin K

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of a vitamin E; and a vitamin K. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of avitamin E; carnitine; and a vitamin K. In other embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; alpha-lipoic acid; and a vitamin K.

In certain embodiments, the disclosure relates to a dietary formulationcomprising: a) medium chain fatty acid, glycerol ester, or alkyl esterthereof, b) an omega-3 fatty acid, alkyl ester thereof, or glycerolester thereof, c) a vitamin E isomer and d) a Vitamin K.

In certain embodiments, the disclosure relates to a dietary formulationcomprising medium chain fatty acid, glycerol ester, or alkyl esterthereof, eicosapentaenoic acid, docosahexaenoic acid, alpha tocopherol,gamma tocopherol, vitamin K, and gamma-linolenic acid.

A “vitamin K” includes vitamin K₁ (phytonadione); Vitamin K₂(menaquinones, e.g., menaquinone-4, menaquinone-7, etc.); Vitamin K₃(menadione; or 2-methyl-1,4-naphthoquinone); a salt of a vitamin K; anda derivative of a vitamin K. In some embodiments, a contemplatedformulation includes vitamin K₁. In other embodiments, a contemplatedformulation includes vitamin K₂. In other embodiments, a contemplatedformulation includes vitamin K₁ and vitamin K₂.

Vitamin K₁ can be present in a subject formulation in an amount of fromabout 100 μg to about 10 mg (total daily dose), e.g., from about 100 μgto about 500 μg, from about 500 μg to about 1 mg, from about 1 mg toabout 2.5 mg, from about 2.5 mg to about 5 mg, from about 5 mg to about7.5 mg, or from about 7.5 mg to about 10 mg.

Vitamin K₂ can be present in a subject formulation in an amount of fromabout 100 μg to about 2 mg (total daily dose), e.g., from about 100 μgto about 250 μg, from about 250 μg to about 500 μg, from about 500 μg toabout 750 μg, from about 750 μg to about 1 mg, from about 1 mg to about1.25 mg, from about 1.25 mg to about 1.5 mg, from about 1.5 mg to about1.75 mg, or from about 1.75 mg to about 2 mg.

S-adenosylmethionine (SAMe)

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of a vitamin E; and S-adenosylmethionine. In someembodiments, a contemplated formulation comprises medium chain fattyacids, or esters thereof; an omega 3 fatty acid or ester; at least oneisoform of vitamin E; carnitine; and S-adenosylmethionine. In someembodiments, a contemplated formulation comprises medium chain fattyacids, or esters thereof; an omega 3 fatty acid or ester; at least oneisoform of a vitamin E; alpha-lipoic acid; and S-adenosylmethionine. Insome embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of a vitamin E; vitamin B₉; and S-adenosylmethionine. Insome embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of a vitamin E; vitamin B₁₂; and S-adenosylmethionine. Insome embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of a vitamin E; vitamin B₉; vitamin B₁₂, andS-adenosylmethionine.

“S-adenosylmethionine” includes2-Amino-4-[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl-methylsulfonio]butanoateand salts thereof. S-adenosylmethionine can be present in a subjectformulation in an amount of from about 50 mg to about 5000 mg, e.g.,from about 100 mg to about 1000 mg, from about 300 mg to about 2000 mg,from about 500 mg to about 3000 mg, from about 1000 mg to about 4000 mg,or from about 400 mg to about 500 mg total daily dose or per unit dose.

Phosphocholine

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of a vitamin E; and a phosphocholine. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; carnitine; and a phosphocholine. In some embodiments, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of a vitamin E;alpha-lipoic acid; and a phosphocholine.

A “phosphocholine” includes phosphatidylcholine derivatives ofphosphocholine, e.g., polyenylphosphatidylcholine. A phosphocholine (ora phosphatidylcholine such as polyenylphosphatidylcholine) can bepresent in a subject formulation in an amount of from about 500 mg toabout 5000 mg, e.g., from about 500 mg to about 1000 mg, from about 1000mg to about 2000 mg, from about 2000 mg to about 3000 mg, from about3000 mg to about 4000 mg, or from about 400 mg to about 5000 mg totaldaily dose or per unit dose.

Coenzyme Q

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of a vitamin E; and a coenzyme Q. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of avitamin E; carnitine; and a coenzyme Q. In other embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of avitamin E; alpha-lipoic acid; and a coenzyme Q.

A “coenzyme Q” (CoQ;2,3-dimethoxy-5-methyl-6-polyprenyl-1,4-benzoquinone; also known asubiquinone) refers to a group of lipid soluble benzoquinones involved inelectron transport in mitochondrial preparations, e.g., in the oxidationof succinate or reduced nicotine adenine dinucleotide (NADH) via thecytochrome system. CoQ includes CoQ_(n), where n is an integer from 1 to12, and where n indicates the number of isoprenoid units. CoQ includes,e.g., CoQ₇₋₁₀, i.e. CoQ₇ (ubiquinone-7), CoQ₉ (ubiquinone-9), CoQ₁₀(ubidecarenone), and mixtures of the foregoing. In some embodiments, theCoQ is ubidecarenone.

A CoQ can be present in a contemplated formulation in an amount of fromabout 4 mg to about 500 mg, from about 4 mg to about 10 mg, from about10 mg to about 25 mg, from about 25 mg to about 50 mg, from about 50 mgto about 75 mg, from about 75 mg to about 100 mg, from about 100 mg toabout 125 mg, from about 125 mg to about 150 mg, from about 150 mg toabout 200 mg, or from about 200 mg to about 500 mg total daily dose orper unit dose.

Creatine

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and creatine. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; carnitine; and creatine. In other embodiments, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of vitamin E;alpha-lipoic acid; and creatine. In other embodiments, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of vitamin E;alpha-lipoic acid; arginine; and creatine. In other embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; alpha-lipoic acid; carnitine; and creatine. In other embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; alpha-lipoic acid; arginine; carnitine; and creatine.

“Creatine” includes 2-[Carbamimidoyl(methyl)amino]acetic acid and saltsthereof. Creatine can be present in a subject formulation in an amountof from about 100 mg to about 30 g, from about 200 mg to about 20 g,from about 500 mg to about 10 g, from about 1000 mg to about 5 g, fromabout 1000 mg to about 3 g.

Taurine

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and taurine. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; carnitine; and taurine. In other embodiments, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of vitamin E;alpha-lipoic acid; and taurine. In other embodiments, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of vitamin E;alpha-lipoic acid; arginine; and taurine. In other embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; alpha-lipoic acid; carnitine; and taurine. In other embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; alpha-lipoic acid; arginine; carnitine; and taurine.

“Taurine” includes 2-aminoethanesulfonic acid and salts thereof. Taurinecan be present in a subject formulation in an amount of from about 20 mgto about 3000 mg, from about 20 mg to about 50 mg, from about 50 mg toabout 100 mg, from about 100 mg to about 250 mg, from about 250 mg toabout 500 mg, from about 500 mg to about 750 mg, from about 750 mg toabout 1000 mg, from about 1000 mg to about 1500 mg, from about 1500 mgto about 2000 mg, from about 2000 mg to about 2500 mg, or from about2500 mg to about 3000 mg.

Berberine

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and berberine. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; carnitine; and berberine. In other embodiments, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of vitamin E;alpha-lipoic acid; and berberine. In other embodiments, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of vitamin E;alpha-lipoic acid; arginine; and berberine. In other embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; alpha-lipoic acid; carnitine; and berberine. In other embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; alpha-lipoic acid; arginine; carnitine; and berberine.

“Berberine” includes the compound5,6-dihydro-9,10-dimethoxybenzo[g]-1,3-benzodioxolo[5,6-a]quinoliziniumand salts thereof. In certain embodiments, berberine may be substitutedwith other like compounds such as sanguinarine, coptisine, goldenseal,and jatrorrhizine. In certain embodiments, berberine can be present in asubject formulation in an amount of from about 100 mg to about 2,000 mg,from about 200 mg to about 1,500 mg, from about 500 mg to about 1,500mg.

Tetrahydrobiopterin

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and tetrahydrobiopterin. In some embodiments,a contemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; carnitine; and tetrahydrobiopterin. In other embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; alpha-lipoic acid; and tetrahydrobiopterin. In other embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; alpha-lipoic acid; arginine; and tetrahydrobiopterin. In otherembodiments, a contemplated formulation comprises medium chain fattyacids, or esters thereof; an omega 3 fatty acid or ester; at least oneisoform of vitamin E; alpha-lipoic acid; carnitine; andtetrahydrobiopterin. In other embodiments, a contemplated formulationcomprises medium chain fatty acids, or esters thereof; an omega 3 fattyacid or ester; at least one isoform of vitamin E; alpha-lipoic acid;arginine; carnitine; and tetrahydrobiopterin.

“Tetrahydrobiopterin” includes 5,6,7,8-tetrahydrobiopterin and saltsthereof; L-erythro-5,6,7,8-tetrahydrobiopterin and salts thereof; andthe like. Tetrahydrobiopterin can be present in a subject formulation inan amount of from about 20 mg to about 3000 mg, from about 20 mg toabout 50 mg, from about 50 mg to about 100 mg, from about 100 mg toabout 250 mg, from about 250 mg to about 500 mg, from about 500 mg toabout 750 mg, from about 750 mg to about 1000 mg, from about 1000 mg toabout 1500 mg, from about 1500 mg to about 2000 mg, from about 2000 mgto about 2500 mg, or from about 2500 mg to about 3000 mg.

Betaine

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and betaine. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; betaine; and pepsin. In some embodiments, a contemplated formulationcomprises medium chain fatty acids, or esters thereof; an omega 3 fattyacid or ester; at least one isoform of vitamin E; carnitine; andbetaine. In other embodiments, a contemplated formulation comprisesmedium chain fatty acids, or esters thereof; an omega 3 fatty acid orester; at least one isoform of vitamin E; alpha-lipoic acid; andbetaine. In other embodiments, a contemplated formulation comprisesmedium chain fatty acids, or esters thereof; an omega 3 fatty acid orester; at least one isoform of vitamin E; alpha-lipoic acid; arginine;and betaine. In other embodiments, a contemplated formulation comprisesmedium chain fatty acids, or esters thereof; an omega 3 fatty acid orester; at least one isoform of vitamin E; alpha-lipoic acid; carnitine;and betaine. In other embodiments, a contemplated formulation comprisesmedium chain fatty acids, or esters thereof; an omega 3 fatty acid orester; at least one isoform of vitamin E; alpha-lipoic acid; arginine;carnitine; and betaine.

“Betaine” includes trimethylglycine and salts thereof and the like.Betaine can be present in a subject formulation in an amount of fromabout 20 mg to about 3000 mg, from about 20 mg to about 50 mg, fromabout 50 mg to about 100 mg, from about 100 mg to about 250 mg, fromabout 250 mg to about 500 mg, from about 500 mg to about 750 mg, fromabout 750 mg to about 1000 mg, from about 1000 mg to about 1500 mg, fromabout 1500 mg to about 2000 mg, from about 2000 mg to about 2500 mg, orfrom about 2500 mg to about 3000 mg.

Pancreatic Enzymes

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and a pancreatic enzyme. Pancreatic enzymesinclude proteases, lipases, amylases, and nucleases. The term“pancreatic enzyme,” as used herein, refers to any enzyme that providesa function (catalytic activity) of an enzyme produced by a humanpancreas. For example, “pancreatic lipase” refers to any enzyme thatprovides a function of a lipase produced by a human pancreas.

In some embodiments, a contemplated formulation includes a lipase, e.g.,a pancreatic lipase. In other embodiments, a subject formulationincludes a pancreatic protease (e.g., trypsin, trypsinogen,chymotrypsin, chymotrypsinogen), and a pancreatic lipase. In otherembodiments, a subject formation includes a pancreatic protease, apancreatic lipase, and a pancreatic amylase.

In some embodiments, the enzyme is an inactive proenzyme (e.g.,trypsinogen, chymotrysinogen). A pancreatic enzyme to be included in aformulation can be a naturally-occurring enzyme, a recombinant enzyme,or a synthetic enzyme; and can be from any of a variety of sources,e.g., a mammal, a fungus, a plant, etc. For example, fungal enzymes, andformulations comprising same, are described in, e.g., U.S. Pat. No.6,051,220. In some embodiments, the enzyme is acid stable, e.g., isstable at a pH range of from about 2.8 to about 9. In some embodiments,the enzyme is in a microencapsulated and enteric coated formulation.Examples of such formulations include, e.g., Cotazym-S, Creon,Pancrease, Pancrease MT-16, Ultrase MT-20, and Zymase. Other suitableformulations include, e.g., a formulation as described in U.S. Pat. No.5,750,104.

The amount of pancreatic enzyme present in a subject formulation canvary, according to need, and can be in a range of from about 2000International Units (IU) to 40,000 IU per unit dose, e.g., from about2000 IU to about 5000 IU, from about 5000 IU to about 7,500 IU, fromabout 7,500 IU to about 10,000 IU, from about 10,000 IU to about 15,000IU, from about 15,000 IU to about 20,000 IU, from about 20,000 IU toabout 30,000 IU, or from about 30,000 IU to about 40,000 IU per unitdose.

Leukotriene Inhibitors

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and a leukotriene inhibitor. Suitableleukotriene inhibitors include leukotriene receptor antagonists andleukotriene synthesis inhibitors. Exemplary leukotriene receptorantagonists include, e.g., zafirlukast (Accolate), montelukast(Singulair), pranlukast, iralukast, pobilukast and SKB-106,203.Leukotriene synthesis inhibitors include inhibitors of 5-lipoxygenaseactivity, where an exemplary 5-lipoxygenase inhibitor is zileuton(Zyflo). Suitable 5-lipoxygenase inhibitors include those described in,e.g., U.S. Pat. Nos. 5,364,877, 5,302,603, 5,234,950, 5,098,932 and5,354,865. In some embodiments, a 5-lipoxygenase inhibitor also inhibitscyclooxygenase-2. In other embodiments, a 5-lipoxygenase inhibitor is aselective 5-lipoxygenase inhibitor, e.g., the inhibitor does notsubstantially inhibit enzymes other than 5-lipoxygenase, e.g., theinhibitor does not substantially inhibit a cyclooxygenase.

The amount of a leukotriene inhibitor that is included in a subjectformulation can vary, depending on factors such as the age and/or weightof the individual to whom the formulation is administered, the severityof symptoms, etc. The amount of a leukotriene inhibitor that is includedin a subject formulation can range from about 2 mg to about 100 mg,e.g., from about 2 mg to about 5 mg, from about 5 mg to about 10 mg,from about 10 mg to about 20 mg, from about 20 mg to about 30 mg, fromabout 30 mg to about 40 mg, from about 40 mg to about 50 mg, from about50 mg to about 60 mg, from about 60 mg to about 70 mg, from about 70 mgto about 80 mg, from about 80 mg to about 90 mg, or from about 90 mg toabout 100 mg per unit dose.

Amino Acids

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and one or more amino acids. For example, insome embodiments, a subject formulation includes arginine, glutamine,N-acetylcysteine, or both arginine and glutamine, or both arginine andN-acetylcysteine, or both glutamine and N-acetylcysteine. If arginineand/or glutamine and/or N-acetylcysteine is present in a formulation,the arginine and/or glutamine and/or N-acetylcysteine is present in anamount of from about 50 mg to about 10 g per unit dose, e.g., from about100 mg to about 750 mg, from about 750 mg to about 1 g, from about 1 gto about 2.5 g, from about 2.5 g to about 5 g, from about 5 g to about7.5 g, or from about 7.5 g to about 10 g. For example, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of vitamin E; andglutamine, the glutamine is present in an amount of from about 50 mg toabout 10 g per unit dose, e.g., from about 100 mg to about 750 mg, fromabout 750 mg to about 1 g, from about 1 g to about 2.5 g, from about 2.5g to about 5 g, from about 5 g to about 7.5 g, or from about 7.5 g toabout 10 g.

As another example, where a contemplated formulation comprises mediumchain fatty acids, or esters thereof; an omega 3 fatty acid or ester; atleast one isoform of vitamin E; and arginine, the arginine is present inan amount of from about 50 mg to about 10 g per unit dose, e.g., fromabout 100 mg to about 750 mg, from about 750 mg to about 1 g, from about1 g to about 2.5 g, from about 2.5 g to about 5 g, from about 5 g toabout 7.5 g, or from about 7.5 g to about 10 g.

As another example, where a contemplated formulation comprises mediumchain fatty acids, or esters thereof; an omega 3 fatty acid or ester; atleast one isoform of vitamin E; and N-acetylcysteine, theN-acetylcysteine is present in an amount of from about 50 mg to about 10g per unit dose, e.g., from about 100 mg to about 750 mg, from about 750mg to about 1 g, from about 1 g to about 2.5 g, from about 2.5 g toabout 5 g, from about 5 g to about 7.5 g, or from about 7.5 g to about10 g.

As another example, where a contemplated formulation comprises mediumchain fatty acids, or esters thereof; an omega 3 fatty acid or ester; atleast one isoform of vitamin E; and both arginine, glutamine, andn-acetylcysteine, the arginine and glutamine and n-acetylcysteine areeach present in an amount of from about 50 mg to about 10 g per unitdose, e.g., from about 100 mg to about 750 mg, from about 750 mg toabout 1 g, from about 1 g to about 2.5 g, from about 2.5 g to about 5 g,from about 5 g to about 7.5 g, or from about 7.5 g to about 10 g.

Anti-Fungal Agents

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and an anti-fungal agent. Suitable anti-fungalagents include, but are not limited to, berberine, nystatin,amphotericin B, clotrimazole, flucytosine, fluconazole, itraconazole,ketoconazole, and noxafil. Where the anti-fungal agent is nystatin, thenystatin can be present in a subject formulation in an amount of fromabout 100,000 Units (U) to about 800,000 Upper unit dose, e.g., fromabout 100,000 U to about 200,000 U, from about 200,000 U to about400,000 U, from about 400,000 U to about 600,000 U, or from about600,000 U to about 800,000 Upper unit dose. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; (e.g., alpha-tocopherol and gamma-tocopherol), carnitine, andnystatin.

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and berberine. In some embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; carnitine; and berberine. In other embodiments, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of vitamin E;alpha-lipoic acid; and berberine. In other embodiments, a contemplatedformulation comprises medium chain fatty acids, or esters thereof; anomega 3 fatty acid or ester; at least one isoform of vitamin E;alpha-lipoic acid; arginine; and berberine. In other embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; alpha-lipoic acid; carnitine; and berberine. In other embodiments, acontemplated formulation comprises medium chain fatty acids, or estersthereof; an omega 3 fatty acid or ester; at least one isoform of vitaminE; alpha-lipoic acid; arginine; carnitine; and berberine.

“Berberine” includes5,6-dihydro-9,10-dimethoxybenzo[g]-1,3-benzodioxolo[5,6-a]quinoliziniumand salts thereof and the like. Berberine can be present in a subjectformulation in an amount of from about 20 mg to about 3000 mg, fromabout 20 mg to about 100 mg, from about 50 mg to about 200 mg, fromabout 100 mg to about 250 mg, from about 250 mg to about 500 mg, fromabout 500 mg to about 750 mg, from about 750 mg to about 1000 mg, fromabout 1000 mg to about 1500 mg, from about 1500 mg to about 2000 mg,from about 2000 mg to about 2500 mg, or from about 2500 mg to about 3000mg.

Anti-Inflammatory Agents

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and an anti-inflammatory agent. Suitableanti-inflammatory agents include, but are not limited to, steroidalanti-inflammatory agents, and non-steroidal anti-inflammatory agents.Suitable steroidal anti-inflammatory agents include, but are not limitedto, hydrocortisone, hydroxyltriamcinolone, alpha-methyl dexamethasone,dexamethasone-phosphate, beclomethasone dipropionate, clobetasolvalerate, desonide, desoxymethasone, desoxycorticosterone acetate,dexamethasone, dichlorisone, diflorasone diacetate, diflucortolonevalerate, fluadrenolone, fluclorolone acetonide, fludrocortisone,flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortinebutylester, fluocortolone, fluprednidene (fluprednylidene) acetate,flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisonebutyrate, methylprednisolone, triamcinolone acetonide, conisone,cortodoxone, flucetonide, fludrocortisone, difluorosone diacetate,fluradrenolone acetonide, medrysone, amcinafel, amcinafide,betamethasone and the balance of its esters, chloroprednisone,chlorprednisone acetate, clocortelone, clescinolone, dichlorisone,difluprednate, flucloronide, flunisolide, fluoromethalone, fluperolone,fluprednisolone, hydrocortisone valerate, hydrocortisonecyclopentylpropionate, hydrocortamate, meprednisone, paramethasone,prednisolone, prednisone, beclomethasone dipropionate, triamcinolone,and mixtures of two or more of the foregoing.

Suitable non-steroidal anti-inflammatory agents, include, but are notlimited to, 1) the oxicams, such as piroxicam, isoxicam, tenoxicam, andsudoxicam; 2) the salicylates, such as aspirin, disalcid, benorylate,trilisate, safapryn, solprin, diflunisal, and fendosal; 3) the aceticacid derivatives, such as diclofenac, fenclofenac, indomethacin,sulindac, tolmetin, isoxepac, furofenac, tiopinac, zidometacin,acematacin, fentiazac, zomepiract, clidanac, oxepinac, and felbinac; 4)the fenamates, such as mefenamic, meclofenamic, flufenamic, niflumic,and tolfenamic acids; 5) the propionic acid derivatives, such asibuprofen, naproxen, benoxaprofen, flurbiprofen, ketoprofen, fenoprofen,fenbufen, indoprofen, pirprofen, carprofen, oxaprozin, pranoprofen,miroprofen, tioxaprofen, suprofen, alminoprofen, and tiaprofenic; and 6)the pyrazoles, such as phenylbutazone, oxyphenbutazone, feprazone,azapropazone, and trimethazone, mixtures of these non-steroidalanti-inflammatory agents may also be employed, as well as thepharmaceutically-acceptable salts and esters of these agents.

Anti-Bacterial Agents

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and an anti-bacterial agent. Suitableanti-antibacterial agents include sulfonamides, diaminopyrimidines,quinolones, beta-lactam antibiotics, cephalosporins, tetracyclines,notribenzene derivatives, aminoglycosides, macrolide antibiotics,polypeptide antibiotics, nitrofuran derivatives, nitroimidazoles,nicotinin acid derivatives, polyene antibiotics, imidazole derivativesor glycopeptide, cyclic lipopeptides, glycylcyclines and oxazolidinones.In further embodiments, these antibiotics include but are not limited tosulphadiazine, sulfones—[dapsone (DDS) and paraaminosalicyclic (PAS)],sulfanilamide, sulfamethizole, sulfamethoxazole, sulfapyridine,trimethoprim, pyrimethamine, nalidixic acids, norfloxacin, ciproflaxin,cinoxacin, enoxacin, gatifloxacin, gemifloxacin, grepafloxacin,levofloxacin, lomefloxacin, moxifloxacin, ofloxacin, pefloxacin,sparfloxacin, trovafloxacin, penicillins (amoxicillin, ampicillin,azlocillin, aarbenicillin, cloxacillin, dicloxacillin, flucloxacillin,hetacillin, oxacillin, mezlocillin, penicillin G, penicillin V,piperacillin), cephalosporins (cefacetrile, cefadroxil, cefalexin,cefaloglycin, cefalonium, cefaloridin, cefalotin, cefapirin,cefatrizine, cefazaflur, cefazedone, cefazolin, cefradine, cefroxadine,ceftezole, cefaclor, cefonicid, ceforanide, cefprozil, cefuroxime,cefuzonam, cefmetazole, cefoteta, cefoxitin, cefcapene, cefdaloxime,cefdinir, cefditoren, cefetamet, cefixime, cefmenoxime, cefodizime,cefoperazone, cefotaxime, cefotiam, cefpimizole, cefpiramide,cefpodoxime, cefteram, ceftibuten, ceftiofur, ceftiolen, ceftizoxime,ceftriaxone, cefoperazone, ceftazidime, cefepime), moxolactam,carbapenems (imipenem, ertapenem, meropenem) monobactams (aztreonam),oxytetracycline, chlortetracycline, clomocycline, demeclocycline,tetracycline, doxycycline, lymecycline, meclocycline, methacycline,minocycline, rolitetracycline, chloramphenicol, amikacin, gentamicin,framycetin, kanamycin, neomicin, neomycin, netilmicin, streptomycin,tobramycin, azithromycin, clarithromycin, dirithromycin, erythromycin,roxithromycin, telithromycin, colistin, bacitracin, tyrothricin,notrifurantoin, furazolidone, metronidazole, tinidazole, isoniazid,pyrazinamide, ethionamide, nystatin, amphotericin-B, hamycin,miconazole, clotrimazole, ketoconazole, fluconazole, rifampacin,lincomycin, clindamycin, spectinomycin, chloramphenicol, clindamycin,colistin, fosfomycin, loracarbef, metronidazole, nitrofurantoin,polymyxin B, polymyxin B sulfate, procain, ramoplanin, teicoplanin, andvancomycin, and combinations thereof.

Anti-Oxidants

In some embodiments, a contemplated formulation comprises medium chainfatty acids, or esters thereof; an omega 3 fatty acid or ester; at leastone isoform of vitamin E; and an agent that reduces oxidative stress,e.g., an anti-oxidant. Suitable anti-oxidants include, but are notlimited to, NXY-059 (Disufenton sodium); chain-breaking phenolicantioxidants (such as Vitamin E and butylated hydroxytoluene [BHT]);phenyl-substituted nitrones; azulenyl-substituted nitrones;alpha-phenyl-N-tert-butyl nitrone; stilbazulenyl nitrone (STAZN; Beckeret al. (2002) J. Am. Chem. Soc. 124:4678); a spin-trap agent such as,e.g., N-t-butyl-a-phenylnitrone, 3,5-dibromo-4-nitrosobenzenesulfonicacid, 5,5-dimethyl-1-pyrroline N-oxide, 2-methyl-2-nitrosopropane,nitrosodisulfonic acid, a-(4-pyridyl-1-oxide)-N-t-butylnitrone,3,3,5,5-tetramethylpyrroline N-oxide, 2,4,6-tri-t-butylnitrosobenzene,PTIYO (4-phenyl-2,2,5,5-tetramethyl imidazolin-1-yloxy-5-oxide), tempol(4-hydroxy 2,2,6,6-tetramethylpiperidine-1-oxyl); and the like. Ananti-oxidant can be a nitrone anti-oxidant (e.g., STAZN), a polyphenolanti-oxidant, a flavonol anti-oxidant (e.g., baicalein), or aphenylpropanoid anti-oxidant (e.g., chlorogenic acid, fisetin, etc.).Also suitable is an anti-oxidant as described in U.S. Patent PublicationNo. 2007/0275932.

Saccharides or Polysaccharides

In certain embodiments, a contemplated formulation comprises mediumchain fatty acids, or esters thereof; an omega 3 fatty acid or ester; atleast one isoform of vitamin E; and a saccharide (e.g., glucose) orpolysaccharide. Such additional components can include, e.g., lactose,glucose, sucrose, corn starch, potato starch, cellulose esters such ascellulose acetate, ethyl cellulose, and microcrystalline cellulose.

Examples of suitable monosaccharides include sorbitol, mannitol,erythrose, threose, ribose, arabinose, xylose, ribulose, glucose,galactose, mannose, fructose, and sorbose. Non-limiting examples ofsuitable disaccharides include sucrose, maltose, lactitol, maltitol,maltulose, and lactose.

Suitable carbohydrates include oligosaccharides, polysaccharides, and/orcarbohydrate derivatives. As used herein, the term “oligosaccharide”refers to a digestible linear molecule having from 3 to 9 monosaccharideunits, wherein the units are covalently connected via glycosidic bonds.As used herein, the term “polysaccharide” refers to a digestible (i.e.,capable of metabolism by the human body) macromolecule having greaterthan 9 monosaccharide units, wherein the units are covalently connectedvia glycosidic bonds. The polysaccharides may be linear chains orbranched. Carbohydrate derivatives, such as a polyhydric alcohol (e.g.,glycerol), may also be utilized as a complex carbohydrate herein. Asused herein, the term “digestible” in the context of carbohydratesrefers to carbohydrates that are capable of metabolism by enzymesproduced by the human body. Examples of non-digestible carbohydrates areresistant starches (e.g., raw corn starches) and retrograded amyloses(e.g., high amylose corn starches). Non-limiting examples of suitablecarbohydrates include raffinoses, stachyoses, maltotrioses,maltotetraoses, glycogens, amyloses, amylopectins, polydextroses, andmaltodextrins.

Suitable starches include natural starches, e.g., starches derived froma natural source, such as those obtained from various plant species.Examples of plant sources of starch include, but are not limited to,corn, waxy corn, wheat, rice, tapioca, potato, pea and other sourcesknown in the art. Suitable starches include modified starches. Modifiedstarches are known in the art and the term generally refers to starchthat has been physically or chemically altered to improve its functionalcharacteristics. Suitable modified starches include, but are not limitedto, pre-gelatinized starches, low viscosity starches (such as dextrins,acid-modified starches, oxidized starches and enzyme modified starches),derivatized starches, stabilized starches (such as starch esters andstarch ethers), cross-linked starches, starch sugars (such as glucosesyrup, dextrose and isoglucose) and starches that have been submitted toa combination of treatments (such as cross-linking and gelatinization)and mixtures thereof.

Suitable modified cellulose gums include, for example, methylcellulose(MC), hydroxypropyl methylcellulose (HPMC), ethyl cellulose (EC),hydroxyethyl cellulose (HEC), hydroxypropylcellulose (HPC),hydroxypropyl methylcellulose acetate, hydroxyethyl methylcellulose,hydroxyethylcellulose acetate, hydroxyethyl ethylcellulose andcombinations thereof.

Food-Grade Components and Pharmaceutically Acceptable Excipients

In certain embodiments, a contemplated formulation comprises mediumchain fatty acids, or esters thereof an omega 3 fatty acid or ester; atleast one isoform of vitamin E; food components and a pharmaceuticallyacceptable excipients. Components such as magnesium stearate, calciumsilicate, precipitated silica, talc, fatty acids such as stearic acid,carnauba wax and the like are contemplated. Diluents and other additivessuch as one or more pharmaceutically acceptable binding agents, fillers,supports, thickening agents, taste-improving agents, coloring agents,preservatives, stabilizers, regulators, emulsifiers, flow agents,absorbents, and the like or mixtures thereof may be used depending onthe form of the composition employed.

In some embodiments, a subject formulation further includes one or morefood-grade components. Suitable components include, but are not limitedto, proteins; amino acids; fatty acids; lipids; stabilizers;preservatives; flavoring agents; coloring agents; sweeteners;antioxidants, chelators, and carriers; texturants; pH adjusters;emulsifiers; stabilizers; soy and soy-based components; milk basesolids; edible fibers; and the like. The food component can be isolatedfrom a natural source, or can be synthesized. All components arefood-grade components fit for human consumption.

In some embodiments, a contemplated formulation that comprises one ormore food components is gluten free. In some embodiments, a contemplatedformulation that comprises one or more food components is casein free.In some embodiments, a contemplated formulation that comprises one ormore food components is gluten free and casein free. “Gluten free” meansthat a subject formulation contains substantially no gluten; or, if theformulation does contain gluten, the gluten is present in an amount thatdoes not induce an adverse reaction in an individual who is glutensensitive (e.g., allergic to gluten) or who is gluten intolerant.Similarly, “casein free” means that a contemplated formulation containssubstantially no gluten; or, if the formulation does contain gluten, thegluten is present in an amount that does not induce an adverse reactionin an individual who is casein sensitive (e.g., allergic to casein) orwho is casein intolerant.

Suitable texturants (also referred to as soluble fibers) include, butare not limited to, pectin (high ester, low ester); carrageenan;alginate (e.g., alginic acid, sodium alginate, potassium alginate,calcium alginate); guar gum; locust bean gum; psyllium; xanthan gum; gumarabic; fructo-oligosaccharides; inulin; agar; a modified cellulose gum;and functional blends of two or more of the foregoing.

Suitable emulsifiers include, but are not limited to, propylene glycolmonostearate (PGMS), sodium stearoyl lactylate (SSL), calcium stearoyllactylate (CSL), monoglycerides, diglycerides, monodiglycerides,polyglycerol esters, lactic acid esters, polysorbate, sucrose esters,diacetyl tartaric acid esters of mono-diglycerides (DATEM), citric acidesters of monoglycerides (CITREM) and combinations thereof. Additionalsuitable emulsifiers include DIMODAN, including DIMODAN™ B 727 andDIMODAN™ PV, GRINDSTED™ CITREM, GRINDSTED™ GA, GRINDSTED™ PS such asGRINDSTED™ PS 100, GRINDSTED™ PS 200, GRINDSTED™ PS 300, GRINDSTED™ PS400; RYLO™ (manufactured and distributed by DANISCO CULTOR), includingRYLO™ AC, RYLO™ CI, RYLO™ LA, RYLO™ MD, RYLO™ MG, RYLO™ PG, RYLO™ PR,RYLO™ SL, RYLO™ SO, RYLO™ TG; and combinations thereof.

Edible fibers include polysaccharides, oligosaccharides, lignin andassociated plant substances. Suitable edible fibers include, but are notlimited to, sugar beet fiber, apple fiber, pea fiber, wheat fiber, oatfiber, barley fiber, rye fiber, rice fiber, potato fiber, tomato fiber,other plant non-starch polysaccharide fiber, and combinations thereof.

Suitable flavoring agents include natural and synthetic flavors, “brownflavorings” (e.g., coffee, tea); dairy flavorings; fruit flavors;vanilla flavoring; essences; extracts; oleoresins; juice and drinkconcentrates; flavor building blocks (e.g., delta lactones, ketones);and the like; and combinations of such flavors. Examples of botanicflavors include, for example, tea (e.g., preferably black and greentea), aloe vera, guarana, ginseng, ginkgo, hawthorn, hibiscus, rosehips, chamomile, peppermint, fennel, ginger, licorice, lotus seed,schizandra, saw palmetto, sarsaparilla, safflower, St. John's Wort,curcuma, cardamom, nutmeg, cassia bark, buchu, cinnamon, jasmine, haw,chrysanthemum, water chestnut, sugar cane, lychee, bamboo shoots,vanilla, coffee, and the like.

Suitable sweeteners include, but are not limited to, alitame; dextrose;fructose; lactilol; polydextrose; xylitol; xylose; aspartame,saccharine, cyclamates, acesulfame K, L-aspartyl-L-phenylalanine loweralkyl ester sweeteners, L-aspartyl-D-alanine amides; L-aspartyl-D-serineamides; L-aspartyl-hydroxymethyl alkane amide sweeteners;L-aspartyl-1-hydroxyethylalkane amide sweeteners; and the like.

Suitable anti-oxidants include, but are not limited to, tocopherols(natural, synthetic); ascorbyl palmitate; gallates; butylatedhydroxyanisole (BHA); butylated hydroxytoluene (BHT); tert-butylhydroquinone (TBHQ); and the like.

Suitable coloring agents include, but are not limited to, FD&C dyes(e.g., yellow #5, blue #2, red #40), FD&C lakes; Riboflavin;beta-carotene; natural coloring agents, including, for example, fruit,vegetable, and/or plant extracts such as grape, black currant, aronia,carrot, beetroot, red cabbage, and hibiscus.

Exemplary Preservatives Include Sorbate, Benzoate, and PolyphosphatePreservatives.

Suitable emulsifiers include, but are not limited to, diglycerides;monoglycerides; acetic acid esters of mono- and diglycerides; diacetyltartaric acid esters of mono- and diglycerides; citric acid esters ofmono- and diglycerides; lactic acid esters of mono- and diglycerides;fatty acids; polyglycerol esters of fatty acids; propylene glycol estersof fatty acids; sorbitan monostearates; sorbitan tristearates; sodiumstearoyl lactylates; calcium stearoyl lactylates; and the like.

Suitable agents for pH adjustment include organic as well as inorganicedible acids. The acids can be present in their undissociated form or,alternatively, as their respective salts, for example, potassium orsodium hydrogen phosphate, potassium or sodium dihydrogen phosphatesalts. Exemplary acids are edible organic acids which include citricacid, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconicacid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid andmixtures thereof.

A contemplated formulation can be prepared in a variety of ways forconsumption by an individual, and, as indicated above, can include oneor more food components. Food formulations can be in a variety of forms,including powders; liquids; gels; and solid forms such as bars, tablets,capsules, candies, etc. Formulations of interest include foods forveterinary or human use, including food bars (e.g. cereal bars,breakfast bars, energy bars, nutritional bars); drinks; fortifieddrinks; carbonated beverages; drink supplements (e.g., powders to beadded to a drink); powders to be mixed with food; tablets; lozenges;candy; candy-like formulations, e.g., chewable gel formulations, e.g.,chewable gel candy in the shape of an animal; puddings; and the like.Suitable food formulations also include those described in U.S. Pat. No.7,067,150.

A food product can have final moisture content between about 0% andabout 100%, e.g., from about 0% to about 1%, from about 1% to about 5%,from about 5% to about 10%, from about 10% to about 30%, from about 30%to about 50%, from about 50% to about 80%, or from about 80% to about100%.

Packages

The present disclosure further provides a package comprising acontemplated formulation. In some embodiments, a contemplated packagecomprises a single dosage form of a contemplated formulation. In otherembodiments, a contemplated package comprises multiple (e.g., 2, 3, 4,5, 6, 7, 8, 9, 10, or more) dosage forms.

As one non-limiting example, a subject food product can be packaged insuch a way that multiple doses are contained in a single package,optionally where individual unit dosage forms are separated inindividual compartments in a single package. The dosage forms can be ina variety of forms, e.g., tablets or lozenges that are palatable (e.g.,flavored so as to be palatable, such as with fruit flavorings, sugars,and the like, as discussed above). Unit dosage forms include tablets,capsules, lozenges, candies, bars, a unit of powder (e.g., 1 tablespoonof a powder; a unit of a liquid, (e.g., a 1 tablespoon of a liquid),etc.

In some embodiments, a contemplated package will further includeinstructions for use, including e.g., dosage amounts and dosagefrequencies. Instructions are in some embodiments printed directly onthe package. In other embodiments, instructions are printed materialprovided as a package insert. Instructions can also be provided in othermedia, e.g., electronically in digital or analogue form, e.g., on anaudio cassette, an audio tape, a compact disc, a digital versatile disk,and the like.

Exemplary Formulations

The following are exemplary formulations. As noted above, in addition tothe components specifically listed below, a contemplated formulation caninclude one or more additional active and/or inactive components,food-grade components, etc. In the exemplary formulations below, amountsare given as per unit dose. In certain embodiments, the components ofthe formulations below (1-30) are in a softgel further comprisinggelatin, purified water and, glycerine. The medium chain fatty acidglycol esters are from Douglas Lab (MCT) liquid approximately caprylic(C8) 70-60% and capric (C10) 40-30%, and less than 5% of other fattyacids.

Exemplary Formulation 1 Exemplary Formulation 2

Component Amount MCT 1000 mg  EPA 700 mg DHA 250 mg Alpha-tocopherol 500mg Gamma-tocopherol 200 mg

Component Amount MCT 10 g  EPA 700 mg DHA 250 mg Alpha-tocopherol 1500mg  Gamma-tocopherol 600 mg

In some embodiments, the amount of MCT in Exemplary formulation 1 isincreased from 1000 mg to 3000 mg.

Exemplary Formulation 3 Exemplary Formulation 4

Component Amount MCT 12 g  EPA 700 mg DHA 250 mg Alpha-tocopherol 500 mgGamma-tocopherol 200 mg Alpha-lipoic acid 100 mg

Component Amount MCT 1000 mg  EPA 700 mg DHA 250 mg Alpha-tocopherol1500 mg  Gamma-tocopherol 600 mg Alpha-lipoic acid 600 mgExemplary Formulation 5 Exemplary Formulation 6

Component Amount MCT 12 g  EPA 700 mg DHA 250 mg Alpha-tocopherol 1500mg  Gamma-tocopherol 600 mg Carnitine 3000 mg 

Component Amount MCT 1000 mg  EPA 700 mg DHA 165 mg Alpha-tocopherol 500mg Gamma-tocopherol 200 mg Carnitine 200 mgExemplary Formulation 7 Exemplary Formulation 8

Component Amount MCT 1000 mg  EPA 700 mg DHA 250 mg GLA  70 mgAlpha-tocopherol 1500 mg  Gamma-tocopherol 600 mg

Component Amount MCT 1000 mg  EPA 700 mg DHA 250 mg GLA  70 mgAlpha-tocopherol 500 mg Gamma-tocopherol 200 mgExemplary Formulation 9 Exemplary Formulation 10

Component Amount MCT 1000 mg  EPA 700 mg DHA 250 mg GLA  70 mg Oleicacid 250 mg Alpha-tocopherol 1500 mg  Gamma-tocopherol 600 mg

Component Amount MCT 1000 mg  EPA 700 mg DHA 250 mg GLA  70 mg Oleicacid 250 mg Alpha-tocopherol 500 mg Gamma-tocopherol 200 mgExemplary Formulation 11 Exemplary Formulation 12

Component Amount MCT 1000 mg  EPA 700 mg DHA 250 mg GLA  70 mg Oleicacid 250 mg Alpha-tocopherol 500 mg Gamma-tocopherol 200 mg Alpha-lipoicacid 100 mg

Component Amount MCT 1000 mg  EPA 700 mg DHA 250 mg GLA  70 mg Oleicacid 250 mg Alpha-tocopherol 1500 mg  Gamma-tocopherol 600 mgAlpha-lipoic acid 600 mgExemplary Formulation 13 Exemplary Formulation 14

Component Amount MCT 1000 mg  EPA 700 mg DHA 250 mg GLA  70 mg Oleicacid 250 mg Alpha-tocopherol 500 mg Gamma-tocopherol 200 mg Alpha-lipoicacid 100 mg Carnitine 200 mg

Component Amount MCT 1000 mg  EPA 700 mg DHA 250 mg GLA  70 mg Oleicacid 250 mg Alpha-tocopherol 1500 mg  Gamma-tocopherol 600 mgAlpha-lipoic acid 600 mg Carnitine 3000 mg Exemplary Formulation 15 Exemplary Formulation 16

Component Amount MCT 1000 mg  EPA 700 mg DHA 250 mg GLA  70 mg Oleicacid 200 mg Alpha-tocopherol 500 mg Gamma-tocopherol 200 mg Alpha-lipoicacid 100 mg Carnitine 1000 mg 

Component Amount MCT 1000 mg  EPA 700 mg DHA 250 mg GLA  70 mg Oleicacid 250 mg Alpha-tocopherol 1500 mg  Gamma-tocopherol 600 mgAlpha-lipoic acid 200 mg Carnitine 3000 mg Exemplary Formulation 17 Exemplary Formulation 18

Component Amount MCT 1000 mg EPA 700 mg DHA 250 mg GLA 70 mg Oleic acid250 mg Alpha-tocopherol 500 mg Gamma-tocopherol 200 mg Alpha-lipoic acid100 mg Carnitine 1000 mg Vitamin C 250 mg

Component Amount MCT 1000 mg EPA 700 mg DHA 250 mg GLA 70 mg Oleic acid250 mg Alpha-tocopherol 1500 mg Gamma-tocopherol 600 mg Alpha-lipoicacid 600 mg Carnitine 3000 mg Vitamin C 500 mgExemplary Formulation 19 Exemplary Formulation 20

Component Amount MCT 1000 mg EPA 700 mg DHA 250 mg GLA 70 mg Oleic acid250 mg Alpha-tocopherol 500 mg Gamma-tocopherol 200 mg Alpha-lipoic acid100 mg Carnitine 200 mg Vitamin C 250 mg Phosphocholine 1 g

Component Amount MCT 1000 mg EPA 700 mg DHA 250 mg GLA 70 mg Oleic acid250 mg Alpha-tocopherol 1500 mg Gamma-tocopherol 600 mg Alpha-lipoicacid 600 mg Carnitine 3000 mg Vitamin C 500 mg Phosphocholine 3 gExemplary Formulation 21 Exemplary Formulation 22

Component Amount MCT 1000 mg EPA 700 mg DHA 250 mg GLA 70 mg Oleic acid250 mg Alpha-tocopherol 500 mg Gamma-tocopherol 200 mg Alpha-lipoic acid100 mg Carnitine 200 mg Vitamin C 250 mg Phosphocholine 1 g Zinc 15 mg

Component Amount MCT 1000 mg EPA 700 mg DHA 250 mg GLA 70 mg Oleic acid250 mg Alpha-tocopherol 1500 mg Gamma-tocopherol 600 mg Alpha-lipoicacid 600 mg Carnitine 3000 mg Vitamin C 500 mg Phosphocholine 3 g Zinc30 mgExemplary Formulation 23 Exemplary Formulation 24

Component Amount MCT 1000 mg EPA 700 mg DHA 250 mg GLA 70 mg Oleic acid250 mg Alpha-tocopherol 500 mg Gamma-tocopherol 200 mg Alpha-lipoic acid100 mg Carnitine 200 mg Vitamin C 250 mg Phosphocholine 1 g Zinc 15 mgVitamin K 5 μg

Component Amount MCT 1000 mg EPA 700 mg DHA 250 mg GLA 70 mg Oleic acid250 mg Alpha-tocopherol 1500 mg Gamma-tocopherol 600 mg Alpha-lipoicacid 600 mg Carnitine 3000 mg Vitamin C 500 mg Phosphocholine 3 g Zinc30 mg Vitamin K 10 mg (K₁ + K₂)Exemplary Formulation 25 Exemplary Formulation 26

Component Amount MCT 1000 mg EPA 700 mg DHA 250 mg GLA 70 mg Oleic acid200 mg Alpha-tocopherol 500 mg Gamma-tocopherol 200 mg Alpha-lipoic acid100 mg Carnitine 500 mg Vitamin C 100 mg Phosphocholine 1 g Zinc 5 mgVitamin K₁ 3 mg Vitamin K₂ 350 μg

Component Amount MCT 1000 mg EPA 700 mg DHA 250 mg GLA 70 mg Oleic acid200 mg Alpha-tocopherol 1500 mg Gamma-tocopherol 500 mg Alpha-lipoicacid 200 mg Carnitine 2000 mg Vitamin C 500 mg Phosphocholine 3 g Zinc15 mg Vitamin K₁ 10 mg Vitamin K₂ 1 mgExemplary Formulation 27 Exemplary Formulation 28

Component Amount MCT 24 g EPA 700 mg DHA 250 mg GLA 70 mg Oleic acid 200mg Alpha-tocopherol 1500 mg Gamma-tocopherol 500 mg Alpha-lipoic acid200 mg Carnitine 2000 mg Vitamin C 500 mg Phosphocholine 3 g Zinc 15 mgVitamin K₁ 10 mg Vitamin K₂ 1 mg Arginine 3000 mg Co-enzyme Q 200 mgSelenium 50 μg Vitamin A 3000 IU Thiamin (B₁) 7.5 mg Riboflavin (B₂) 7.5mg Vitamin B₆ 200 mg Vitamin B₁₂ 1 mg Vitamin D 400 IU Calcium 100 mgElemental magnesium 200 mg Biotin (B₇) 50 μg Folic acid 400 μgPantothenic acid 10 mg Tetrahydrobiopterin 50 mg Niacin 15 mg

Component Amount MCT 10 g Icosapent ethyl (ethyl ester 1 g ofeicosapentaenoic acid) Alpha-tocopherol 1500 mg Gamma-tocopherol 500 mgBerberine 400 mg Creon (porcine-derived 6,000 USP units of lipaselipases, proteases, and 19,000 USP units of protease amylases) 30,000USP units of amylase Starch 50 gExemplary Formulation 29 Exemplary Formulation 30

Component Amount MCT 10 g EPA 700 mg DHA 250 mg GLA 70 mg Oleic acid 200mg Alpha- tocopherol 1500 mg Gamma- tocopherol 500 mg Alpha- lipoic acid200 mg Carnitine 2000 mg Vitamin C 500 mg Phosphocholine 3 g Zinc 15 mgVitamin K₁ 10 mg Vitamin K₂ 1 mg Arginine 3000 mg

MCT 2 g alpha tocopheral 500 IU Gamma tocopheral 200 mg Vitamin K (K1and K2) 2.3 mg EPA 725 mg DHA 275 mg GLA 60 mg Co-enzyme Q 200 mgSelenium 50 μg Vitamin A 3000 IU Thiamin (B₁) 7.5 mg Riboflavin (B₂) 7.5mg Vitamin B₆ 200 mg Vitamin B₁₂ 1 mg Vitamin D 400 IU Calcium 100 mgMagnesium citrate 200 mg Biotin (B₇) 50 μg Folic acid 400 μg Pantothenicacid 10 mg Tetrahydrobiopterin 50 mg Niacin 15 mg N-acetylcysteine 200mg Acetylsalicylic acid 100 mg Methylcobalamin 1 mg Folinic acid 800 μgBerberine 400 mg Creon (porcine-derived 6,000 USP units of lipaselipases, proteases, and 19,000 USP units of protease amylases) 30,000USP units of amylaseExemplary Formulation 31

MCT (1000 mg); EPA (700 mg); DHA (250 mg); Alpha-tocopherol (50 mg);Gamma- tocopherol (20 mg); Sodium Citrate (100 mg); PotassiumBicarbonate (300 mg); glucose (35 g); L-amino acids of L-Glutamine,L-Lysine Acetate, L-Leucine, L-Arginine Acetate, L-Valine, L-Isoleucine, L-Aspartic Acid, L-Alanine, L-Phenylalanine, L-Serine,L-Proline, L-Threonine, L- Tyrosine, L-Glutamic Acid, L-HistidineHydrochloride, L-Methionine, L-Cystine, and L- Tryptophan (mixture of 6g); β-carotene (400 μg); L-ascorbic acid (25 mg); Calcium carbonate (500mg); Iron (mg 10); Cholecalciferol (10 μg); Phylloquinone (15 μg);Thiamin (1 mg); Riboflavin (1 mg); Niacin (5 mg); Pyridoxine (1 mg);Folic Acid (50 μg); Cobalamin (1 μg); Biotin (30 μg); Pantothenic Acid(2 mg); Calcium phosphate (300 mg); Iodine (30 μg; Magnesium sulfate(100 mg); Zinc gluconate (5 mg); Selenium Ascorbate (μg 10); Cupricsulfate (1 mg) Manganese citrate (1 mg), Chromium Acetate (20 μg);Molybdenum Citrate (20 μg); L-Carnitine (6 mg); Taurine (20 mg); Choline(60 mg), and myo-inositol (20 mg).

A contemplated formulation can be prepared as a single dosage form, ordivided into two or more dosage forms. A contemplated formulation cancomprise one unit dose; two unit doses; three unit doses; or more thanthree unit doses. For example, any of exemplary formulations 1-31 can bedivided into two or more capsules, two or more tablets, two or morebars, two or more units of a powder (e.g., two or more grams of apowder, two or more tablespoons of a powder, etc.), two or more unitsliquid (e.g., two or more 1-ml units of a liquid, two or more 5-mL unitsof a liquid, etc.), two or more chewable gel units, or two or more unitsof another dosage form. Alternatively, a contemplated formulation can bea liquid formulation, where it can be formulated in a single dose (e.g.,1-15 mL) or formulated such that it is administered in two or moredoses, where each dose is 1-10 mL). For example, exemplary formulations1-31 provide the unit doses of the various components, which can beadministered to an individual in one, two, three, four, or more, doses,which doses can be in various dosage forms, e.g., tablets, capsules,liquids, powders, food products, etc.

Methods of Use

In certain embodiments, the disclosure relates to methods of treating orpreventing apraxia and/or autism spectrum disorder, the methodcomprising orally administering to an individual in need thereof aneffective amount of a dietary formula disclosed herein. In certainembodiments, the disclosure relates to methods the subject is diagnosedwith intestinal lymphangiectasia.

In certain embodiments, the intestinal lymphangiectasia is not occurringin isolation but together with the symptoms of apraxia/dyspraxia/autismspectrum disorders—symptoms which dramatically improve with aggressivenutrition particularly with omega 3 and fat soluble vitamins andminerals (zinc/magnesium) and medium chain acids and esters disclosedherein.

In certain embodiments, the disclosure relates to methods theformulation is administered once, twice, or three times daily, whereinsaid administration is effective to increase the percentile score of atleast one of oral movement score, simple phonemic/syllabic score,complex phonemic/syllabic score, and spontaneous length and complexityscore, by at least about 10, 20 or 30 percentile points.

In certain embodiments, the disclosure relates to methods of treating orpreventing small bowel inflammation and conditions lending to smallbowel bacterial overgrowth that induce fat malabsorption, the methodcomprising orally administering to an individual in need thereof aneffective amount of a dietary formula disclosed herein to a subject inneed thereof.

In certain embodiments, the disclosure relates to methods of treating anallergic disorder, the method comprising orally administering to anindividual in need thereof an effective amount of the formulationdisclosed herein wherein the disorder is selected from celiac disease,sprue, gluten sensitivity, a malabsorption syndrome, asthma, foodallergy, leaky gut syndrome, and/or eczema.

In certain embodiments, the disclosure relates to methods of treating aninflammatory condition, the method comprising orally administering to anindividual in need thereof an effective amount of a dietary formuladisclosed herein, wherein the inflammatory condition is small intestinalbacterial overgrowth, rheumatic arthritis, diabetes, or cardiovasculardisease.

In certain embodiments, the disclosure relates to methods of treating orpreventing malnutrition and verbal apraxia or dyspraxia by administeringeffective amounts of nutritional formulas disclosed herein to a subjectin need thereof. In certain embodiments, the subject is diagnosed withan autism spectrum disorder and intestinal lymphangiectasia, e.g., byvideo capsule endoscopy.

The present disclosure provides methods of treating various disorders,involving administering to an individual in need thereof an effectiveamount of a contemplated formulation. In certain embodiments, the methodis useful for treating various disorders, including, but not limited to,apraxia, dyspraxia, autism, autism spectrum disorder, attentiondeficit/hyperactivity disorder, dyslexia, depression, sensoryintegration dysfunction; immune system disorders such as celiac disease,sprue, gluten sensitivity, a malabsorption syndrome, asthma, foodallergy, leaky gut syndrome, and eczema; cardiovascular disease;diabetes; and inflammatory conditions such as rheumatoid arthritis.

In some embodiments, the method comprises administering a formuladisclosed herein to an individual with apraxia, to treat the apraxia. Inthese embodiments, an effective amount of a subject formulation is anamount that, when administered in one or more doses, is effective toprovide for an improvement in one or more of an oral movement score, asimple phonemic/syllabic score, a complex phonemic/syllabic score, and aspontaneous length and complexity score, e.g., in the Kaufman PraxisTest. For example, an effective amount of a subject formulation is anamount that, when administered in one or more doses, is effective toprovide for an increase in percentile score of from about 5 to about 10percentile, from about 10 to about 20 percentile, from about 20 to about40 percentile, from about 40 to about 60 percentile, from about 60 toabout 70 percentile, or from about 70 to about 90 percentile, on one ormore of an oral movement score, a simple phonemic/syllabic score, acomplex phonemic/syllabic score, and a spontaneous length and complexityscore, e.g., in the Kaufman Praxis Test. Whether a subject formulationis effective in treating a disorder such as apraxia can be determinedusing well-established tests, such as the Kaufman Praxis Test.

A contemplated formulation is in some embodiments administered to anindividual with an immune system disorder, to treat the immune systemdisorder. In these embodiments, an effective amount of the formulationis an amount that, when administered in one or more doses, is effectiveto provide for a reduction in one or more symptoms of an immune systemdisorder. For example, where the immune system disorder is an allergicdisorder, an effective amount of a formulation is an amount that, whenadministered in one or more doses, is effective to provide for areduction in circulating factor that is an indicator of an allergicdisorder of from about 10% to about 20%, from about 20% to about 25%,from about 25% to about 30%, from about 30% to about 40%, from about 40%to about 50%, from about 50% to about 60%, from about 60% to about 70%,or from about 70% to about 80%, or more, of the level of the circulatingfactor present following exposure to an allergy-stimulating allergen.Circulating factors that are indicators of an allergic disorder include,e.g., allergen-specific IgE; inflammatory biomarkers; C-reactiveprotein; cytokines that are indicative of a Th2 immune response; and thelike. As another example, where the immune system disorder is anallergic disorder, an effective amount of a formulation is an amountthat, when administered in one or more doses, is effective to providefor one or more of: i) clinical improvement in one or more of sneezing,wheezing, runny nose, and other symptoms of an allergic reaction; ii)decreased number of visits to a medical personnel for treatment for theallergic disorder; and iii) decreased use of medications used to treatthe symptoms of an allergic disorder. Whether a subject formulation iseffective in treating an immune system disorder such as an allergicdisorder can be determined using any well-established test, e.g.,immunoassays for measuring IgE levels (e.g., allergen-specific IgElevels), and the like.

A contemplated formulation is administered, e.g., orally, to anindividual in need thereof in any frequency deemed appropriate to treatthe condition or disorder. For example, a formulation can beadministered three times daily, twice daily, once daily, every otherday, three times per week, twice per week, once per week, or less often.In some embodiments, a formulation is administered daily. In otherembodiments, a formulation is administered every other day. For example,a unit dose of a contemplated formulation can be administered once,twice, or three times daily.

A contemplated formulation can be administered at any frequency, asdiscussed above, over any period of time, as necessary to treat thecondition or disorder. Thus, a formulation can be administered over aperiod of time, e.g., from about one week to about one month, from aboutone month to about three months, from about three months to about 6months, from about 6 months to about one year, from about one year toabout three years, from about three years to about six years, from aboutsix years to about 10 years, or more than 10 years.

The dosages of medium chain fatty acids and esters (glycerol esters),omega 3 fatty acids or esters, and vitamin E, as well as the dosages ofadditional components such as carnitine and alpha-lipoic acid, can varyaccording to various factors, including, e.g., the age of theindividual, the weight of the individual, the genetic makeup of theindividual, and the severity of symptoms exhibited by the individual towhom a subject formulation is administered. The following are generalguidelines.

Where a subject formulation includes medium chain fatty acids and esters(glycerol esters), the dosage may ranges from about 100 mg/day to about5000 mg/day, e.g., from about 100 mg/day to about 200 mg/day, from about200 mg/day to about 300 mg/day, from about 300 mg/day to about 400mg/day, from about 400 mg/day to about 500 mg/day, from about 500 mg/dayto about 600 mg/day, from about 600 mg/day to about 700 mg/day, fromabout 700 mg/day to about 800 mg/day, from about 800 mg/day to about 900mg/day, from about 900 mg/day to about 1000 mg/day, from about 1000mg/day to about 1100 mg/day, from about 1100 mg/day to about 1200mg/day, from about 1200 mg/day to about 1300 mg/day, from about 1300mg/day to about 1400 mg/day, from about 1400 mg/day to about 1500mg/day, from about 1500 mg/day to about 2000 mg/day, from about 2000mg/day to about 3000 mg/day, from about 3000 mg/day to about 4000mg/day, from about 4000 mg/day to about 5000 mg/day, from about 5 g/dayto about 10 mg/day, from about 5 g/day to about 10 mg/day, from about 10g/day to about 20 mg/day, from about 20 g/day to about 50 mg/day wherethe dosages given are for individual medium chain fatty acids or estersthereof or for total medium chain fatty acids or esters thereof (e.g.,where more than one medium chain fatty acid glycol ester is present).

Where a subject formulation includes omega-3 fatty acids, the dosage ofthe omega-3 fatty acids ranges from about 100 mg/day to about 5000mg/day, e.g., from about 100 mg/day to about 200 mg/day, from about 200mg/day to about 300 mg/day, from about 300 mg/day to about 400 mg/day,from about 400 mg/day to about 500 mg/day, from about 500 mg/day toabout 600 mg/day, from about 600 mg/day to about 700 mg/day, from about700 mg/day to about 800 mg/day, from about 800 mg/day to about 900mg/day, from about 900 mg/day to about 1000 mg/day, from about 1000mg/day to about 1100 mg/day, from about 1100 mg/day to about 1200mg/day, from about 1200 mg/day to about 1300 mg/day, from about 1300mg/day to about 1400 mg/day, from about 1400 mg/day to about 1500mg/day, from about 1500 mg/day to about 2000 mg/day, from about 2000mg/day to about 3000 mg/day, from about 3000 mg/day to about 4000mg/day, or from about 4000 mg/day to about 5000 mg/day, where thedosages given are for individual omega-3 fatty acids or for totalomega-3 fatty acids (e.g., where more than one omega-3 fatty acid ispresent).

For example, in some embodiments, a contemplated formulation comprisesthe medium chain triglycerides which are the glycol esters of caprylicacid and capric acid, omega-3 fatty acids EPA and DHA. In someembodiments, the glycol esters glycol esters of caprylic acid and capricacid will range from about 50 mg/day to about 40 g/day, e.g., from about500 mg/day to about 30 g/day, from about 1000 mg/day to about 20 g/day,from about 1000 mg/day to about 10 g/day, from about 2000 mg/day toabout 10 mg/day, or from about 1000 mg/day to about 5 g/day.

In some embodiments, the dosage for EPA will range from about 500 mg/dayto about 3000 mg/day, e.g., from about 500 mg/day to about 600 mg/day,from about 600 mg/day to about 700 mg/day, from about 700 mg/day toabout 800 mg/day, from about 800 mg/day to about 900 mg/day, or fromabout 900 mg/day to about 1000 mg/day; and the dosage of DHA will rangefrom about 100 mg/day to about 1000 mg/day, e.g., from about 100 mg/dayto about 150 mg/day, from about 150 mg/day to about 200 mg/day, fromabout 200 mg/day to about 250 mg/day, from about 250 mg/day to about 300mg/day, from about 300 mg/day to about 350 mg/day, from about 350 mg/dayto about 400 mg/day, from about 400 mg/day to about 500 mg/day, fromabout 500 mg/day to about 600 mg/day, from about 600 mg/day to about 700mg/day, from about 700 mg/day to about 800 mg/day, from about 800 mg/dayto about 900 mg/day, or from about 900 mg/day to about 1000 mg/day.

The dosage of alpha-tocopherol ranges from about 10 mg/kg/day to about200 mg/kg/day, e.g., from about 10 mg/kg/day to about 25 mg/kg/day, fromabout 25 mg/kg/day to about 50 mg/kg/day, from about 50 mg/kg/day toabout 75 mg/kg/day, from about 75 mg/kg/day to about 100 mg/kg/day, fromabout 100 mg/kg/day to about 125 mg/kg/day, from about 125 mg/kg/day toabout 150 mg/kg/day, from about 150 mg/kg/day to about 175 mg/kg/day, orfrom about 175 mg/kg/day to about 200 mg/kg/day; and the dosage ofgamma-tocopherol ranges from about 100 mg/day to about 1000 mg/day,e.g., from about 100 mg/day to about 200 mg/day, from about 200 mg/dayto about 300 mg/day, from about 300 mg/day to about 400 mg/day, fromabout 400 mg/day to about 500 mg/day, from about 500 mg/day to about 600mg/day, from about 600 mg/day to about 700 mg/day, from about 700 mg/dayto about 800 mg/day, from about 800 mg/day to about 900 mg/day, or fromabout 900 mg/day to about 1000 mg/day.

The dosage of other forms of vitamin E (e.g., beta-tocopherol,delta-tocopherol, alpha-tocotrienol, beta-tocotrienol,delta-tocotrienol, and gamma-tocotrienol), if present in a subjectformulation, can range from about 5 mg/day to about 1000 mg/day, e.g.,from about 5 mg/day to about 10 mg/day, from about 10 mg/day to about 25mg/day, from about 25 mg/day to about 50 mg/day, from about 50 mg/day toabout 75 mg/day, from about 75 mg/day to about 100 mg/day, from about100 mg/day to about 125 mg/day, from about 125 mg/day to about 150mg/day, from about 150 mg/day to about 175 mg/day, from about 175 mg/dayto about 200 mg/day, from about 200 mg/day to about 250 mg/day, fromabout 250 mg/day to about 500 mg/day, from about 500 mg/day to about 750mg/day, or from about 750 mg/day to about 1000 mg/day, where the dosagesgiven are for the individual isoforms of vitamin E.

Where a subject formulation comprises one or more omega-6 fatty acids,the dosage of omega-6 fatty acid can range from about 50 mg/day to about1000 mg/day, e.g., from about 50 mg/day to about 75 mg/day, from about75 mg/day to about 100 mg/day, from about 100 mg/day to about 150mg/day, from about 150 mg/day to about 200 mg/day, from about 200 mg/dayto about 250 mg/day, from about 250 mg/day to about 300 mg/day, fromabout 300 mg/day to about 350 mg/day, from about 350 mg/day to about 400mg/day, from about 400 mg/day to about 450 mg/day, from about 450 mg/dayto about 500 mg/day, from about 500 mg/day to about 600 mg/day, fromabout 600 mg/day to about 700 mg/day, from about 700 mg/day to about 800mg/day, from about 800 mg/day to about 900 mg/day, or from about 900mg/day to about 1000 mg/day.

Where a subject formulation comprises one or more omega-9 fatty acids,the dosage of omega-9 fatty acid can range from about 50 mg/day to about500 mg/day, e.g., from about 50 mg/day to about 75 mg/day, from about 75mg/day to about 100 mg/day, from about 100 mg/day to about 150 mg/day,from about 150 mg/day to about 200 mg/day, from about 200 mg/day toabout 250 mg/day, from about 250 mg/day to about 300 mg/day, from about300 mg/day to about 350 mg/day, from about 350 mg/day to about 400mg/day, from about 400 mg/day to about 450 mg/day, or from about 450mg/day to about 500 mg/day.

Where a subject formulation comprises alpha-lipoic acid, the dosage ofalpha-lipoic acid can range from about 10 mg/kg/day to about 50mg/kg/day, e.g., from about 10 mg/kg/day to about 20 mg/kg/day, fromabout 20 mg/kg/day to about 25 mg/kg/day, from about 25 mg/kg/day toabout 30 mg/kg/day, from about 30 mg/kg/day to about 40 mg/kg/day, orfrom about 40 mg/kg/day to about 50 mg/kg/day; or can range from about50 mg/day to about 1000 mg/day, e.g., from about 50 mg/day to about 75mg/day, from about 75 mg/day to about 100 mg/day, from about 100 mg/dayto about 150 mg/day, from about 150 mg/day to about 200 mg/day, fromabout 200 mg/day to about 250 mg/day, from about 250 mg/day to about 300mg/day, from about 300 mg/day to about 350 mg/day, from about 350 mg/dayto about 400 mg/day, from about 400 mg/day to about 450 mg/day, fromabout 450 mg/day to about 500 mg/day, from about 500 mg/day to about 600mg/day, from about 600 mg/day to about 700 mg/day, from about 700 mg/dayto about 800 mg/day, from about 800 mg/day to about 900 mg/day, or fromabout 900 mg/day to about 1000 mg/day.

Where a subject formulation comprises carnitine, the dosage of carnitinecan range from about 20 mg/kg/day to about 75 mg/kg/day, e.g., fromabout 20 mg/kg/day to about 25 mg/kg/day, from about 25 mg/kg/day toabout 30 mg/kg/day, from about 30 mg/kg/day to about 30 mg/kg/day, fromabout 40 mg/kg/day to about 50 mg/kg/day, from about 50 mg/kg/day toabout 60 mg/kg/day, or from about 60 mg/kg/day to about 75 mg/kg/day; orcan range from about 150 mg/day to about 3000 mg/day, e.g., from about150 mg/day to about 200 mg/day, from about 200 mg/day to about 250mg/day, from about 250 mg/day to about 300 mg/day, from about 300 mg/dayto about 350 mg/day, from about 350 mg/day to about 400 mg/day, fromabout 400 mg/day to about 450 mg/day, from about 450 mg/day to about 500mg/day, from about 500 mg/day to about 600 mg/day, from about 600 mg/dayto about 700 mg/day, from about 700 mg/day to about 800 mg/day, fromabout 800 mg/day to about 900 mg/day, from about 900 mg/day to about1000 mg/day, from about 1000 mg/day to about 1250 mg/day, from about1250 mg/day to about 1500 mg/day, from about 1500 mg/day to about 1750mg/day, from about 1750 mg/day to about 2000 mg/day, from about 2000mg/day to about 2250 mg/day, from about 2250 mg/day to about 2500mg/day, from about 2500 mg/day to about 2750 mg/day, or from about 2750mg/day to about 3000 mg/day.

Subjects Suitable for Treatment

Subjects suitable for treatment with a subject method includeindividuals who have been diagnosed with a disorder such as apraxia,dyspraxia, autism spectrum disorder, intestinal lymphangiectasia, agastrointestinal disorder, small intestinal bacterial overgrowth,attention deficit/hyperactivity disorder, dyslexia, or depression,sensory integration dysfunction; or an immune system disorder such asceliac disease, sprue, gluten sensitivity, a malabsorption syndrome,asthma, food allergy, leaky gut syndrome, or eczema; a cardiovasculardisease; diabetes; or an inflammatory condition such as rheumatoidarthritis. Subjects suitable for treatment with a subject method alsoinclude individuals who have been previously treated (with a treatmentmethod other than a subject method) for a disorder such as those listedabove, but who have failed treatment (e.g., failed to respond to thetreatment), who have relapsed, or in whom the previous treatment methodwas contraindicated (e.g., due to adverse reaction, etc.).

In some embodiments, the individual is a sub-adult human, e.g., aninfant (e.g., from about 1 month of age to about 12 months of age); atoddler (e.g., from about 12 months of age to about 3 years of age); apre-school age child (e.g., from about 3 years of age to about 5 yearsof age); a child from about 5 years of age to about 9 years of age; apre-teen from about 9 years of age to about 12 years of age; or ateenager (e.g., from about 13 years of age to about 19 years of age). Inother embodiments, the individual is an adult human, e.g., a human atleast 18-20 years old.

In some embodiments, the individual is a sub-adult human who has beendiagnosed with apraxia. In some embodiments, the individual is asub-adult human who has been diagnosed with autism spectrum disorder. Incertain embodiments, the subject has attention deficit hyperactivitydisorder or any type of inflammatory bowel disease (IBD) such as Crohn'sdisease and ulcerative colitis.

In some embodiments, the individual exhibits gluten sensitivity. In someembodiments, the individual has a human leukocyte antigen (HLA) allelethat is associated with gluten sensitivity. For example, in someembodiments, the individual has an HLA DQ1 allele. In some embodiments,the individual has elevated levels of anti-gliadin antibodies.

EXAMPLES Child with ADS Diagnosed with Intestinal Lymphangiectasia

A child diagnosed with an apraxia syndrome responded to omega 3fatty-acid and vitamin E supplementation. Small intestinallymphangiectasia was recently discovered on video-capsule endoscopy aspart of the continuing work-up for malabsorption. Intestinallymphangiectasia is characterized by obstruction of lymph drainage fromthe small intestine and lacteal dilation that distorts the villusarchitecture (See FIG. 1). Lymphatic vessel obstruction and elevatedintestinal lymphatic pressure in turn cause lymphatic leakage into theintestinal lumen, thus resulting in malabsorption and protein-losingenteropathy. Intestinal lymphangiectasia is believed to be a “rare”condition. It is believed that, intestinal lymphangiectasia has not beenreported in children with autism and/or apraxia. The pathology in thesmall intestine would commonly be missed by conventional endoscopy.

The immune dysfunction caused by intestinal lymphangiectasia could leadto increased risk of opportunistic infections, explaining chronic thrushbeyond infancy, disseminated molluscum infection, recurrent skininfections, and difficult to treat recurrent small bowel bacterialovergrowth an additional condition that will contribute to malabsorptionand malnutrition. It would also explain remarkable anecdotal reports ofdramatic improvements in speech, neuro-cognitive abilities and motorcoordination with nutritional interventions.

The white villi and/or spots (dilated lacteals), white nodules in thejejunum are observed on video capsule endoscopy are consistent with thediagnosis of intestinal lymphangiectasia. This taken together with along-standing history of fat malabsorption, neurological symptoms ofvitamin E deficiency, a protein-losing enteropathy with previouslyunexplained hypoalbuminemia, multiple micronutrient and vitamindeficiencies (zinc, iron, vit D, B12 etc), short stature, edema of theankles and hands, hypocholesterolemia (cholesterol<100), andvulnerability to infections suggesting immune dysregulation (chronicthrush, disseminated molluscum contagiosum, recurrent skin, ear andsinus infections) explains the dramatic response to nutritionalinterventions in this child.

Speech, coordination, hypotonia and pain sensation improved dramaticallywith omega 3, medium chain triglycerides, and vitamine Esupplementation. Further benefits were realized with a comprehensivenutritional approach which included supplementation for vitamins andminerals found to be deficient, treatments aimed at small intestinebacterial overgrowth, antifungals for thrush, amino acid supplements,creatine (patient had h/o low creatine), carnitine/mitochondrialcocktail (alpha lipoic acid, Co-Q10, B-vitamins, vitamin C), pancreaticenzymes and anti-inflammatory therapies that target inflammatory boweldisease. Since the protein malnutrition and nutritional deficiencieswere numerous, due to the small bowel disease, a comprehensivenutritional approach led to significant recovery of growth and weightgain and improved neurobehavioral issues typical of apraxia as well asimproved nutritional status.

An adequate gastrointestinal work-up is rarely done in children withautism and/or apraxia despite symptoms of pain, diarrhea/constipation,fat malabsorption and immune issues (frequent infections). Conventionalendoscopy would miss it in the distal small intestine (jejunum orileum). However intestinal lymphangiectasia would explain GI symptoms,fat malabsorption, vitamin and mineral deficiencies and frequentinfections that many of these children are afflicted by. It alsoprovides a plausible explanation for clinical improvements withaggressive nutrition.

This disclosure contemplates an improved nutritional supplementformulated to treat or prevent intestinal lymphangiectasia, and incertain instances children diagnosed with autism and a speechimpediment. Given that intestinal lymphangiectasia is worsened byingestion of fat that dilate the lacteals, a high quality protein, lowfat diet is typically recommended. However low-fat diets for childrencan contribute to essential fatty acid deficiencies that can lead toadverse neuro-cognitive and behavior complications.

In certain embodiments, this disclosure relates to a nutritional formulacomprising long-chain polyunsaturated fatty acids, medium chaintriglycerides, and fat soluble vitamins (fat-soluble vitamins A, D, Eand K) to overcome the fat malabsorption syndrome. Optionallyingredients include carnitine, alpha lipoic acid, co-Q10, B-vitamins andminerals such as zinc, magnesium, calcium. In certain embodiments, thenutritional formula further comprises a saccharide or polysaccharide,such as purified glucose. In certain embodiments, the nutritionalformula further comprises amino acids including glutamine and all or anyessential/non-essential amino acids, taurine, probiotics, creatine, SAMe(S-adenosylmethionine), berberine, n-acetylcysteine, andtrimethylglycine.

Elemental Amino Acid Formula

One uses formulations with MCT, omega-3s, and vitamin E in combinationwith a nutritionally complete hypoallergenic, amino acid-based infant &pediatric formula (non-peptide/protein) that includes essentialnutrients. This can be used as a supplement for the dietary managementof protein maldigestion, malabsorption, intestinal lymphangiectasia,GI-tract impairment, small bowel bacterial overgrowth etc. or otherconditions in which an amino acid-based diet is required—that hasadditional ingredients beyond the essential amino acids, that includepoly unsaturated fatty acids (DHA/EPA etc), higher dose of vitamine E tomaximize neurological development & function that is compromised inconditions of malabsorption/SIBO, and additional ingredients to aiddigestion (pancreatic enzymes), address an abnormal gut microbiome(probiotics, berberine), and address inflammation and/or oxidativestress (curcumin, Sulforaphane, etc). There is an unmet need for thesepatients.

This formulation typically contains essential vitamins, micronutrients,amino acids and fats such as monosaccharides (glucose), Medium ChainTriglycerides (from Coconut and/or Palm Kernel Oil), Soybean Oil,Calcium Glycerophosphate, Magnesium Gluconate and less than 2% ofL-Glutamine, L-Lysine Acetate, L-Leucine, L-Arginine Acetate, PotassiumChloride, L-Valine, Citric Acid, L-Isoleucine, L-Aspartic Acid,L-Alanine, L-Phenylalanine, L-Serine, L-Proline, L-Threonine, SodiumCitrate, L-Tyrosine, L-Glutamic Acid, Potassium Citrate, Glycine,L-Histidine Hydrochloride, L-Methionine, Choline Bitatrate, L-Cystine,Polyglycerol Esters of Fatty Acids, L-Tryptophan, Sodium Phosphate,Ascorbic Acid, Potassium Sorbate and BHA/BHT (to Maintain Freshness),M-Inositol, Taurine, Alpha-Tocopheryl Acetate, Ferrous Sulfate,L-Carnitine, Zinc Sulfate, Niacinamide, Calcium Pantothenate, VitaminD3, Copper Gluconate, Vitamin A Palmitate, Manganese Sulfate, PyridoxineHydrochloride, Thiamine Hydrochloride, Riboflavin, Beta Carotene,Chromium Chloride, Sodium Molybdate, Folic Acid, Potassium Iodide,Biotin, Sodium Selenite, Phytonadione, Vitamin B12.

For example one can add to commercially available formulas of Vivonexand EleCare poly unsaturated fatty acids (DHA/EPA etc), higher dose ofvitamin E to maximize neurological development & function that iscompromised in conditions of malabsorption/SIBO, and additionalingredients to aid digestion (pancreatic enzymes), address an abnormalgut microbiome (probiotics, berberine), and addressinflammation/oxidative stress (curcumin, Sulforaphane, etc) optionallywith higher vitamin/mineral doses and optionally additional ingredientsthat support mitochondrial function (co-Q10/Lipoic Acid/Carnitine/highdose vit E/B complex), or ingredients that addressinflammation/oxidative stress (sulforaphane, e.g., derived from broccolisprouts), curcumin, or the abnormal gut microbiome (berberine).

The invention claimed is:
 1. A method of treating autism spectrumdisorder comprising orally administering daily to a subject diagnosedwith an autism spectrum disorder, apraxia, and a gastrointestinal tractimpairment, an effective amount of a dietary formulation comprising: a)a medium chain fatty acid, glycerol ester, or alkyl ester thereof, b) anomega-3 fatty acid, glycerol ester, or alkyl ester thereof, c) anomega-6 fatty acid, glycerol ester, or alkyl ester thereof, and d) avitamin E isomer from 100 mg to 10,000 mg, e) 5-hydroxytryptophan, from10 mg to 100 mg, f) sulforaphane from 500 micrograms to 5000 micrograms,and g) curcumin from 50 mg to 2500 mg; and wherein the dietaryformulation comprises less than 2% long chain saturated fatty acids byweight of the total weight of fatty acids.
 2. The method of claim 1,wherein the gastrointestinal tract impairment is intestinallymphangiectasia.
 3. The method of claim 1, wherein the gastrointestinaltract impairment is maldigestion.
 4. The method of claim 1, wherein thegastrointestinal tract impairment is malabsorption.
 5. The method ofclaim 1, wherein the gastrointestinal tract impairment is smallintestinal bacterial overgrowth.
 6. The method of claim 1, wherein thesubject is a sub-adult from 12 months to 19 years of age.
 7. The methodof claim 6, wherein the sub-adult is from about 12 months of age toabout 3 years of age.
 8. The method of claim 6, wherein the sub-adult isfrom 3 years of age to 5 years of age.
 9. The method of claim 6, whereinthe sub-adult is 5 years of age to 9 years of age.
 10. The method ofclaim 6, wherein the sub-adult is 9 years of age to 12 years of age. 11.The method of claim 6, wherein the sub-adult is 13 years of age to 19years of age.
 12. The method of claim 1, wherein the medium chain fattyacid or alkyl ester thereof is capric acid, ethyl caprate, caprylicacid, ethyl caprylate, hexanoic acid, ethyl hexanoate, or combinationsthereof.
 13. The method of claim 1, wherein the dietary formulationfurther comprises a vitamin K.
 14. The method of claim 1, wherein theomega-3 fatty acid or alkyl ester thereof is alpha-linolenic acid,eicosapentaenoic acid, docosahexaenoic acid, ethyl linolenate, ethyleicosapentaenoate, ethyl docosahexaenoate, or combinations thereof. 15.The method of claim 1, wherein the omega-3 fatty acid containseicosapentaenoic acid and docosahexaenoic acid.
 16. The method of claim15, wherein a ratio of eicosapentaenoic acid and docosahexaenoic acid isin a range of from about 1.5:1 to about 5:1.
 17. The method of claim 1,wherein the vitamin E isomer is alpha-tocopherol, gamma-tocopherol, or acombination thereof.
 18. The method of claim 1, wherein the omega-6fatty acid is gamma-linolenic acid.
 19. The method of claim 1, whereinthe dietary formulation comprises less than 1% long chain saturatedfatty acids by weight of the total weight of fatty acids.